Can McIlroy overcome his swing issues in tandem with new coach Pete Cowen and find a way to contend? Will Dustin Johnson repeat his dominant victory five months ago? Can Bryson DeChambeau power his way to victory, or will a resurgent Jordan Spieth continue his winning form?
And what are Lee Westwood's chances of finally making his major breakthrough at the age of 47? Here's how the first major of the year could play out...
It's still hard to fathom how, after winning his fourth major at the 2014 PGA Championship, Rory McIlroy has not added to that tally in the six years since hoisting the Wanamaker Trophy for the second time at Valhalla.
A month previously, he had also had his name etched below the greats of the game on the Claret Jug following a convincing Open triumph at Royal Liverpool, thus landing the third of the four major titles. All that remained was a Green Jacket, and surely winning the Masters was a matter of "when", and not "if"?
Six failed attempts at completing the Grand Slam later, questions remain over McIlroy's ability to get the job done at Augusta National, a course which should be ideally suited to his style of play. But the issue here is more psychological than physical.
McIlroy has spoken openly and honestly about his struggles in the Masters, not that six top-10 finishes over the last seven years could be classed as "struggles" for mere mortals. Time and again, he has described the "mental hurdle" he has to clamber over to earn a seat and a natter with Jim Nantz in the Butler Cabin.
He'll deny it, but even 10 years on, it is almost certain that McIlroy continues to be haunted by his infamous back-nine meltdown when leading the Masters midway through Sunday afternoon. Yes, he bounced back in the very next major and destroyed the field to win the US Open in record-breaking style at Congressional, but every time he pitches up at Augusta, much of the pre-tournament hype is focused on his Grand Slam aspirations.
It's impossible to avoid, and clearly a distraction, and McIlroy has tried everything in terms of preparation - both competitively and in his mindset - in order to clear that final hurdle. And every year he doesn't manage that, it gets a notch tougher the following year.
And now, he has added focus on him after his revelations following a poor performance at The Players last month. His swing was faltering, he admitted that, when he got to the top of his backswing, he had little idea of where the ball was going. But how did it get to this?
The faults developed during speed training sessions last autumn, a course of action he conceded was influenced by the manner of Bryson DeChambeau's thumping win at the US Open. McIlroy has since turned to Pete Cowen in an effort to get him back on track, and that extra length could be useful at Augusta. But what is more useful is getting his wedges closer to the pins, and putting less pressure on his putting.
It's difficult to see him contending this week, but who knows. The extra work on the range, with a new coach, might be a welcome distraction from the usual "will he or won't he" focus of the Grand Slam bid.
He still has plenty of time on his side, and he'll know the value of patience and persistence. It worked for Sergio, after all!
Jack Nicklaus, Nick Faldo and Tiger Woods. Three legends of golf, and the only three players to have successfully defended the Masters. That's a measure of how tough a task it is to go back-to-back at Augusta National.
But, for Dustin Johnson this year, the circumstances are different, and in his favour. Having cruised to a handsome five-shot victory in November, he returns to defend his title just five months later. As unfair as it might seem to be the reigning Masters champion for not even half a year, the main benefit for Johnson is that the memories of his second major win are still fresh, and he is in roughly the same form.
And he's still world No 1... by some distance!
We've seen many Masters champs who have played themselves into a rut thereafter, and instead of thinking about contending for the title a year later, they're hosting the annual Tuesday Masters Club Dinner distracted by the fear of missing the halfway cut and having to hang around for the weekend to help a new champion into a new Green Jacket. But Johnson's second start after his Augusta triumph was another win, again taming a world-class field at the Saudi International.
DJ will not be fazed by the weight of history against him, and he would, no doubt, be delighted to shed tears in public again as he takes his victory photocall. And if he does get that chance again, he has the added bonus of a few thousand patrons in attendance to share his euphoria.
The talk started barely a few minutes after he had won the US Open, blitzing the field by six shots using the "bomb and gouge" tactics that many had predicted would prove his undoing on a track like Winged Foot. The conversation ahead of the Masters was not necessarily if Bryson DeChambeau would win, but by how much?
And how many scoring records would he break? And statistical records? And will he put that new driver, with the 48-inch shaft, in his bag and reduce 14 holes at Augusta National to a drive and a wedge? As it transpired, it was none of the above.
In fact, DeChambeau finished one shot behind 63-year-old Bernhard Langer, who was a two-time Masters champion before the American was born! But Bryson had endured worrying health problems during the tournament, and his explanation for his illness was suitably out of the ordinary.
"I went to multiple doctors trying to figure out what it was," he said in January. "I got a couple of MRIs, I went to an inner-ear doctor, had eye tests and ear tests, and they even did ultrasounds on my heart and neck. But one thing I will tell you is I've done a lot of brain training, and the frontal lobe of my brain was working really, really hard. That's what gave me some weird symptoms. It was like crazy overworking.
"It all took a toll. I don't think it was exactly that specific thing. But it was a combination of a few things that escalated my brain, overworking and just giving out."
So, there you have it. If Bryson wants to win the Masters, he has to stop overloading his brain! But after his exploits at Bay Hill, trying to drive the green at the par-five sixth, he proved beyond reasonable doubt that he captivates golf fans - and sports fans - like no other current player.
Whatever he does at Augusta National, and he'll surely be a factor if he can avoid illness, it will be entertaining to watch. Although maybe not so much for the Masters committee!
It doesn't seem that long ago that Jordan Spieth was an automatic contender for the Masters every year. In fact, he was short odds for every major, no matter what the venue, but the Masters was where he truly excelled. His first three trips to Augusta National? Second, first, second! And he went close again in 2018 as he and Rickie Fowler pushed Patrick Reed to the wire.
Spieth's victory in 2015 was about as dominant as they come, opening with a 64 that was three shots better than anyone else in the field, and back-to-back 70s over the weekend were enough for a four-shot win that some felt could have been double the winning margin had he really been pressed.
The young Texan then won the US Open, albeit with a little help from DJ, he was right up there in the mix at The Open and the PGA, and on his return to Augusta in 2016, he was on course to better his winning margin from the previous year - five clear at the turn on Sunday.
And then he rinsed two balls in Rae's Creek at the 12th and, while Danny Willett was not complaining, that seemed to set the American back for a while. But he then answered his critics with an astonishing final five holes to win The Open at Royal Birkdale in 2017.
In January this year, the former world No 1 was on the verge of dropping out of the world's top 100. But a superb week in Phoenix began to turn his fortunes around, and he kept it going at Pebble Beach and led going into the final round two weeks running.
He was right up there again at Bay Hill, putting like the Spieth of old and looking far more consistent and confident from tee to green. He just needed to stop using up the vast majority of his good fortune on a Saturday and save some gems for Sundays!
And that he did, in some style, when he landed his first win in almost four years in his home state. At the start of the year, Spieth's odds for the Masters were not far off those of when he made his debut. After the Players Championship, those odds had shortened to 14/1. Winning the Valero Texas Open saw him arrive at Augusta on Monday with an extra spring in his step, and rated by Sky Bet as the third favourite at 10/1 behind only Dustin Johnson and Bryson DeChambeau.
He's arrived at Augusta before, without any form to speak of, and contended. Imagine what he can do when in form! Dismissing Spieth's chances at the Masters is like dismissing the prospect of a successful Tiger Woods comeback. Never rule out Spieth at Augusta, never.
Lee Westwood, like Colin Montgomerie, has spent much of his career saddled with the unenviable tag of "best player never to have won a major". But the way he's been playing over the last 18 months, he will head to Augusta National with every chance of passing on that label.
Watching him go head-to-head with big Bryson at Bay Hill was a joy, and proof enough that the Englishman still has what it takes - and more - to compete with golf's elite on the big stage.
The Masters has always been a good fit for Westwood, now 47, and he knows how to get around Augusta despite its length appearing unsuitable for the seasoned campaigners to cope with.
He is the reigning European No 1, he's comfortably inside the top 50 in the world rankings, and he has a relaxed demeanour about him both on and off the course, looking every inch like a man enjoying his golf - and life in general.
Just after he was crowned Race to Dubai champion in December, Rob Lee wrote: "It wouldn't be a life-changing event for Lee to win a major, he's had plenty of success both individually and for Europe in the Ryder Cup, but a major would be an endorsement of just how brilliant he's been throughout his career.
"I'm not going to say it's too late for him to make that major breakthrough now. He is still highly rated by his peers worldwide. He's an extraordinary player who's had an extraordinary career, but if I could grant him one wish for 2021, it would be that elusive major win.
"I'm absolutely certain and convinced that Westwood will have another good crack at a major, maybe more than once. It's up to him to defy history and get over the line, but you cannot rule it out".
The veteran went close in a superb two weeks in Florida, at Bay Hill and then The Players, being paired with DeChambeau in the final group of the final round in both, and there was suddenly a lot of love for his chances at the Masters, where he has six top-10 finishes - two of them as runner-up.
Lee John Westwood in a Green Jacket? You'd have to be pretty cold-hearted to begrudge him that honour.