Title-holder Roger Federer and Serb Novak Djokovic will be hoping to have recovered from their energy-sapping ordeals as they aim to set up a high-profile meeting in the last four at the US Open.
Both players will need to be on their guard against in-form opponents in Thursday's quarter-finals with Federer taking on Gilles Mueller of Luxembourg and Djokovic facing big-serving American favourite Andy Roddick.
Second seed Federer, seeking his fifth consecutive title at Flushing Meadows but his first grand slam crown of the year, is well aware of the danger posed by unseeded Mueller.
Mueller upset fifth-seeded Russian Nikolay Davydenko on his way to the last eight and knocked out Roddick in the first round in 2004 when the American was the defending champion.
"I'm definitely aware of how well he's playing," Federer said of a player ranked 130th in the world. "I saw a little bit how he plays. He played aggressive. Serves well. He didn't beat Andy for nothing here a few years ago.
"That's why I definitely won't underestimate him because he's a good player," added the Swiss, who scraped past Russian Igor Anrdeev in five sets in the fourth round.
Djokovic will need to shake off the inevitable soreness that has built up after a gruelling four-set clash with Marin Cilic in round three followed by a testing five-set clash with Spanish 15th seed Tommy Robredo.
The third-seeded Serbian, who won his first grand slam title in Australia at the beginning of this year, will face another tough examination of his title credentials when he takes on Roddick, the eighth seed.
The American has returned to form after a disappointing build-up to the Open and will undoubtedly be the fresher having lost just one set in his four matches.
"He's a former US Open champion, couple of times a grand slam finalist and a former number one," Djokovic said.
"He's playing in front of his crowd, in his favourite tournament. It's always a difficult one to play against Roddick wherever, but especially here."