Sixteen third round ties are being played on Tuesday and Wednesday with Chelsea facing Newcastle United, Stoke City playing Fulham, Sunderland hosting West Ham United, Aston Villa playing Blackburn Rovers and West Bromwich Albion facing Manchester City in the other all-Premier League ties.
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Holders Manchester United, who beat Aston Villa in last season's final and are bidding for a hat-trick of wins in the competition, play at Championship Scunthorpe United on Wednesday, the first ever meeting between the clubs.
The outstanding game though is the north London derby between Spurs and Arsenal, even though Spurs manager Harry Redknapp and his Arsenal counterpart Arsene Wenger will be shuffling their sides because of Champions League commitments.
Redknapp told reporters at a media briefing at Spurs training ground north of London on Monday that he will give a debut to Croatian goalkeeper Stipe Pletikosa, on loan from Spartak Moscow, and Sandro.
A highly-promising central midfielder who made his debut for Brazil last year, Sandro was chased by a host of clubs before signing for Spurs.
"He's just come from a tough season in Brazil where Internacional won the championship," said Redknapp.
"He's a 6-foot-2 inches (1.87 metres) tall central midfield player, he's in the Brazilian squad, he's only 21 and a boy still - but you don't get too many bad players breaking into the Brazil national squad so its a good chance to see him play now."
Redknapp said he also thought that Spurs were closing the gap on their fiercest rivals whose Emirates ground is only three miles (five kilometres) away from White Hart Lane.
"Arsenal have been more successful in recent years for sure, but we are getting closer. When we get our new stadium we will be getting 60,000 every week the same as Arsenal, we are both massive clubs."
Spurs beat Arsenal 5-1 for a 6-2 aggregate victory in the semi-final of the League Cup in January 2008 and beat them 2-1 at White Hart Lane in April, their first Premier League win over them for 11 years.
Tuesday's match will not feature many of the players who appeared in April as Redknapp said he was going to make big changes from the side that beat Wolverhampton Wanderers 3-1 on Saturday.
"We've got lots of players who need to play and it gives me a chance to give them a game and I need to rest some of the lads who have played so many games," he said.
"There will be lots of changes but Arsene has done it, played the young players, even in semi-finals, against Tottenham and against Chelsea in a final, so I have to do what's right for Tottenham. I've got to protect the players for the Premier League and Champions League games."
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