Ronaldo left Madrid for Juventus earlier this summer to bring an end to his illustrious nine-year stay in the Spanish capital, which saw him score a club-record 450 goals in just 438 appearances.
Such mind-boggling numbers are surely impossible to replace, but Ronaldo's absence does open the door for someone else to become the main man at the Bernabeu, and Gareth Bale is at the front of that queue.
The Welsh winger's last competitive club outing saw him come off the bench to score twice - including arguably the greatest Champions League final goal of all time - to steer Madrid to the trophy for a third successive season, and he has been promised an even bigger role under new boss Julen Lopetegui.
Here, Sports Mole looks at how Bale has fared against Atletico in the past.
Atletico's defence is famously miserly under Diego Simeone, but even accounting for that it is surprising to see that Bale has scored only once in his 16 previous meetings with Real's city rivals.
That goal was an important one - putting Real ahead in extra time of the 2013-14 Champions League final - but since then Bale has gone 10 matches without finding the back of the net against Atletico.
The winger has registered six assists against Atletico down the years, including one in the 2015-16 Champions League final and one in the most recent meeting between the two sides, but he has generally found things more difficult against La Rojiblancos.
Indeed, Bale has a losing record against Atletico overall, winning just four of his 16 meetings across all competitions, and only one in eight previous La Liga clashes.
Real have never been beaten by Atletico when Bale has directly contributed to a goal, though, so if he can get off the mark for the season in Tallinn then it would be a promising omen for Los Blancos.