Below, we have taken a look at the most pertinent Opta facts ahead of the first grand slam of 2018.
Williams, not prone to droughts herself, last played last January in winning the 2017 Australian Open, and gave birth to her daughter last September 1.
No Australian man has won the Australian Open since Mark Edmondson in 1976, and no woman since Chris O'Neil in 1978.
Federer got the better of his opponent on that occasion and the Swiss will be strongly fancied to retain his title this year as he chases yet another entry into the history books.
It was Nadal's fifth tiebreak in three days at the venue, after he headlined the Tiebreak Tens event on Wednesday night.
Annacone believes that Federer proved the doubters wrong, after failing to win a major title for four years from 2013 before taking two in 2017: the Australian Open and Wimbledon, where he became the oldest victor in the modern era at 35.
Should Djokovic come through that, he could face France's former world No 6 Gael Monfils, who enters the Australian Open as the recently-crowned Qatar Open champion - a tournament Djokovic has twice won but opted to miss this year to continue his recovery.
The Serb is now languishing at a lowly 14th world ranking, having been on a six-month hiatus due to an elbow injury that required surgery. "I don't think there's anybody else that you could say is a favourite other than Roger at the moment".
The first Grand Slam of the year is just around the corner - but who can threaten the usual suspects in the Australian Open men's singles? However, the current season will be made more hard by the return of Novak Djokovic and Stan Wawrinka, who missed the 2017 campaign through injury. When both departed before the quarter-finals, it cleared the way for Roger Federer and Rafael Nadal to reach the final.
2008 champion Maria Sharapova will begin her campaign against World No. 46 Tatjana Maria and the top seed and World No. 1 Simona Halep has the rising Australian Destanee Aiava in the opening round.
"He could always get picked off early", McEnroe said.
Like many players, injuries plagued Kyrgios' 2017, but in front of a willing home crowd at Melbourne Park, the right-hander will be desperate to put on a dazzling display.
Second seed Caroline Wozniacki will open her tournament against Romania's Mihaela Buzarnescu, while third seed Garbine Muguruza takes on French wildcard Jessika Ponchet.
She is yet to drop a set over six matches in qualifying or the main draw and will next meet world number 22 Kerber who staged a 6-3 6-1 victory over Dominika Cibulkova in the last eight.