The pair clashed in the semi-finals of the competition last season, with Dortmund advancing 4-3 on aggregate. Dortmund did lose 2-0 in the Spanish capital, but a 4-1 victory in the first leg in Germany was enough for Jurgen Klopp's side to book their spot at Wembley.
The European rivals also met in the group stages last season, with Dortmund winning their home group match 2-1, before drawing 2-2 in the Bernabeu. Klopp's side twice led in Spain, but goals from Pepe and Mesut Ozil ensured that Madrid picked up a point.
Madrid, who are in the last eight for the fourth successive season, overcame Schalke 04 in the last-16 stage of the competition. Overall, their record against German opposition is strong with 19 wins from their 25 matches – losing just twice in the process.
Carlo Ancelotti's side enter the match having lost two of their last three games, however, with defeats in La Liga to Barcelona and Sevilla leaving the capital outfit in third spot in the table.
Dortmund, meanwhile, have lost two of their last five in all competitions. They overcame Zenit St Petersburg in the previous round despite losing the second leg 2-1 on their own patch.
The German side's overall record in Spain is poor, meanwhile, with just one win and six defeats from their 11 matches. Their only win in Spain arrived in the 1996-97 campaign, when they overcame Atletico Madrid 1-0 in the group stages of the competition.
Los Blancos will be without the services of long-term absentees Jese Rodriguez, Alvaro Arbeloa and Sami Khedira for the clash at the Bernabeu, but head coach Ancelotti has no fresh concerns from the 5-0 win over Rayo Vallecano in the league at the weekend.
The big team news for Dortmund, meanwhile, is the absence of suspended striker Robert Lewandowski. Jakub Błaszczykowski, Marcel Schmelzer, Neven Subotic and Sven Bender are also unavailable, but Marco Reus will feature.
Possible starting lineups
Madrid: Casillas; Carvajal, Pepe, Ramos, Marcelo; Modric, Alonso, Di Maria; Ronaldo, Benzema, Bale
Dortmund: Weidenfeller; Piszczek, Hummels, Papastathopoulos, Durm; Kehl, Sahin, Groskreutz; Reus, Mkhitaryan, Aubameyang
Sports Mole says: 3-1