Newly-crowned German champions Bayern Munich will face Spanish giants Barcelona in the semi-finals of the Champions League.
Bayern, who lost last season's final on their own ground to Chelsea, will bid to make their second consecutive final at Wembley on May 25 but they must first defeat Barca, who will make a record sixth successive semi-final appearance.
Real Madrid, semi-finalists for a record 24th time and in the final four for the third successive season, will face Borussia Dortmund and have the advantage of playing the second leg of their semi-final at home.
The draw at UEFA's headquarters in Nyon, Switzerland, kept the two German and two Spanish sides apart, meaning there will not be a repeat of three seasons ago when Primera Division rivals Barcelona and Real Madrid met in the semi-finals.
However, even though Real have avoided an El Clasico showdown in the final four, they will instead face a determined Dortmund side who they failed to beat during this season's group stages.
Dortmund, who have made the semi-finals for the first time in 15 years, are the only unbeaten side left in the competition, which includes a Group D 2-1 home win against Real before they drew 2-2 in the reverse fixture at the Bernabeu.
Bayern will play Barcelona on 23 April and May 1, while Dortmund and Real will face each other on April 24 and 30.
Bayern chairman Karl-Heinz Rummenigge admits he is relishing a tough test against a side he holds in such high regard
"Barcelona are the benchmark for me in Europe. They have won the Champions League more than any other team in the recent years," Rummenigge told UEFA's website.
"They are the best team in Europe at the moment with fantastic attacking potential.
"We played them in 2009 and received a real thumping. I remember that game well and I don't really like to think about it, because it was quite painful to watch.
"However, it's a wonderful opportunity to show that we have improved a lot since then."
Rummenigge also denied that playing the opening match at home is a disadvantage.
"I think we will see two very good games played at the highest possible level," he said.
"Furthermore, I think playing at home first is a slight advantage, contrary to the popular belief that it's a disadvantage.
"We saw that against Juventus, where people said that it might be a disadvantage. But we produced a great performance at home and that set the stage for the return leg and our progression into the semi-finals.
"I'm really excited that we will get to play the best team in Europe. I still feel Barcelona are the big favourites to win the Champions League."
Meanwhile, Dortmund general manager Hans-Joachim Watzke was pleased to have drawn a Spanish opponent and avoid an all-Bundesliga tie.
"We are happy with this draw - not because we think it's an easy one, but because the Champions League is an international competition and we wanted an international game rather than a national tie against Bayern," Watzke said.
"I don't think Madrid will be afraid because of what happened in the group stage.
"They will respect us, just like we will respect them."
Real manager Jose Mourinho, who has guided the Spanish side to their third successive semi-final, has matched Manchester United boss Sir Alex Ferguson's record of seven appearances in the last four of the European Cup.
The Portuguese has also reached this stage with Porto, Inter Milan and Chelsea.
Former Real striker and club ambassador Emilio Butragueno insisted Dortmund will not be taken lightly, even though they have been absent from the final stages of the tournament for a decade and a half.
"It's a pleasure and honour for us to be here," Butragueno said.
"We have a lot of respect for Borussia Dortmund. We played them twice (in the group stage) but didn't manage to beat them.
"This time we hope it will different as we want to be in the final, that's what we are all dreaming of."
Bayern Munich v Barcelona
Borussia Dortmund v Real Madrid