Liverpool, Aston Villa and Stoke City will be among those hoping to avoid being the victim of a giant-killing this weekend as the FA Cup reaches the third-round stage.
The Premier League sides join the competition and as history shows, it is prime time for smaller sides looking for a big upset.
Liverpool travel to Exeter City of League Two on Friday night in decent form but with an injury list so extensive that they may be forced to play some of their youth team.
Kolo Toure is the only established centre back who is not on the treatment table and even he finished Tuesday’s League Cup semi-final at Stoke suffering from cramps.
Manager Juergen Klopp admits the injury situation means he will not be able to rotate his squad in the usual manner, which might open the door to Exeter, although they have lost four games in a row.
Exeter manager Paul Tisdale said the match is a chance for his side to express themselves.
“We have to appreciate the differences but play our own game,” he told a pre-match press conference.
“It’s going to be a League Two mid-winter pitch and it will be different to what Liverpool are used to but I don’t want to come off it thinking we’ve left it short.
“The reality is it’s a game where we’ve got everything to gain and nothing to lose - and I hope we’ve given it a good shot at the end.”
Villa are in huge trouble in the Premier League, bottom of the table with just eight points from 20 matches and staring relegation in the face.
A trip to League Two side Wycombe Wanderers is probably the last thing they would like and Wycombe midfielder Matt Bloomfield believes his side have a real opportunity.
“They’ve got a team full of players bought for millions of pounds,” the Get Bucks website quoted him as saying.
“They may be having a tough time of it at the moment, but they are still very good players who you have to respect.
“If they turn up on the day and play to their maximum then they should win the game, but at the end of the day it’s 11 versus 11.
“If we can play above our potential and they dip below theirs, we may have a chance.”
Stoke travel to Doncaster Rovers of League One in the middle of an impressive season but on the back of two defeats, at West Bromwich Albion and at home to Liverpool.
Manager Mark Hughes will be looking for an immediate response from his players but his opposite number, Darren Ferguson believes anything is possible on the day.
“Mark’s done a fabulous job and they’ve got a big squad but it’s a good challenge for our lads to look forward to,” he told the Doncaster Free Press.
“It’ll be a different kind of challenge, totally different. It’s a game in which I might be able to try one of two things differently but it’s up to us to go for that cup shock.
“That’s what the competition is all about - and you would think there will be an upset or two on Saturday.”