Real travel to White Hart Lane brimming with confidence after demolishing Spurs 4-0 in the first leg of their quarter-final last week, while Barca go to Shakhtar Donetsk in Ukraine 5-1 up.
Barring the most unlikely of events, Real and Barca will meet each other in European competition for the first time since 2002.
Real coach Jose Mourinho, publicly at least, has paid Spurs and English football the greatest respect by saying only an English team could overturn a four-goal deficit.
If that is true, then that club are Spurs, who have dazzled in their debut season in the Champions League with some stunning fightbacks and re-kindled a flickering light from the past.
After Manchester United, Spurs were English soccer's trailblazers in Europe in the early 1960s when they became the first British side to win a European trophy, beating Atletico Madrid 5-1 in the European Cup Winners' Cup final in 1963.
A year earlier Spurs reached the semi-finals of the European Cup when their manager Bill Nicholson, paying his respects to the all-conquering Real team of Alfredo Di Stefano and Ferenc Puskas, decided his team should change to an all-white kit for European games.
Real, some years later, became the first away team in 24 years ever to win a European tie at White Hart Lane when they beat holders Spurs 1-0 in the UEFA Cup in 1985 - and are easily equipped to score another win on Wednesday.
However, although Spurs are almost certain to go out, they will not go down without showing the spirit that has been a feature of their Champions League adventure which ended almost before it started back in August.
Spurs were 3-0 down after 28 minutes of the first leg of their qualifying play-off against Young Boys in Berne before losing 3-2 and then qualifying for the group stage with a 4-0 win in the second leg in London.
In the group stage they were losing 4-0 at halftime to holders Inter Milan before a Gareth Bale hat-trick in the second half pulled the score back to 4-3. Spurs then beat Inter 3-1 in the return in London.
Spurs manager Harry Redknapp said: "It has been a great experience so far and I am sure it will be a great experience on Wednesday. We will give it our best shot and see what happens."
They will have to do that without striker Peter Crouch, sent off last week, while Real Madrid will be without the suspended Pepe.
Mourinho, though, can also call on Karim Benzema in attack after his recovery from an injury he suffered playing for France, and he could replace Emmanuel Adebayor, whose two headers last week set Real on their way to their emphatic win.
Possible teams:
Tottenham Hotspur: 1-Heurelho Gomes; 32-Benoit Assou-Ekotto, 4-Younes Kaboul, 20-Michael Dawson, 22-Vedran Corluka; 3-Gareth Bale, 14-Luka Modric, 8-Jermaine Jenas, 11-Rafael van der Vaart; 18-Jermain Defoe, 9-Roman Pavlyuchenko
Real Madrid: 1-Iker Casillas; 4-Sergio Ramos, 18-Raul Albiol, 2-Ricardo Carvalho, 12-Marcelo; 14-Xabi Alonso, 24-Sami Khedira; 22-Angel Di Maria, 23-Mesut Ozil, 7-Cristiano Ronaldo; 9-Kar
