Atletico have been Barcelona's closest challengers in the league this season, but their defeat at Real Betis last weekend means that Los Blancos have the chance to rise into second position in Spain's top flight.
There is no question that Madrid have turned a corner in recent weeks, and they will enter this match off the back of an excellent result against Barcelona in the first leg of their Copa del Rey quarter-final on Wednesday.
Indeed, a 1-1 draw at Camp Nou has placed Madrid as the favourites ahead of the second leg, with Lucas Vazquez on the scoresheet for Santiago Solari's side, who have only lost one of their last nine games in all competitions.
Here, Sports Mole takes a look at how Los Blancos could line up against Atletico.
Jesus Vallejo and Enzo Zidane are still out for Madrid with hamstring problems, while Marcos Llorente will miss the derby this weekend with the groin injury that he suffered against Barcelona.
It seems likely that Solari will make changes following the Barcelona clash, meaning that Marco Asensio and Gareth Bale are both in contention to feature. Neither has been too impressive since returning from injury, but 18-year-old Vinicius Junior has played a lot of football in recent weeks.
Karim Benzema will be looking to continue his excellent run of form, meanwhile, having found the back of the net on 18 occasions this season, including three in his last two in the league.