Both sides were locked in a 1-1 draw earlier this season at the BayArena in what proved to be Peter Bosz's penultimate Bundesliga game in charge at Dortmund. But draws are often hard to come by when Leverkusen and Dortmund go head to head, sharing the points just 10 times in 36 meetings since the turn of the century.
Here's everything you need to know about the clash this Saturday:
Ousmane Dembélé continued the fine form he had shown throughout his maiden year in Germany by opening the scoring after just six minutes, and fellow Dortmund bad boy Pierre-Emerick Aubameyang doubled their lead before the half time whistle.
But a seemingly routine win for the hosts was turned on its head just three minutes after the restart when Kevin Volland found the back of the net. Even Aubameyang's second goal of the game didn't deter Leverkusen, with Wendell responding directly from a free kick.
Christian Pulisic then scored Borussia Dortmund's fourth goal of the match to finally end any hopes of a late comeback, before André Schürrle and Raphaël Guerreiro added the gloss to a stellar performance from the Black and Yellows.
Joel Pohjanpalo will be out of action once more this weekend for Bayer Leverkusen and their only other injury concern is with Brazilian left back Wendell, who is still recovering from torn ligaments.
Potential Borussia Dortmund Starting Lineup: Bürki, Piszczek, Toprak, Sokratis, Schmelzer, Weigl, Dahoud, Pulisic, Reus, Philipp, Schürrle.
This game is set up perfectly to be one of the last great Bundesliga fixtures before the end of the season, with both Dortmund and Leverkusen level on points in the league table.
On top of that, both sides are looking to bounce back after defeats in their last game. Dortmund lost on the road to local rivals Schalke 04, while Leverkusen were dumped out of the DFB-Pokal in a 6-2 defeat at the hands of Bayern Munich.
Despite being away from home this weekend, Leverkusen will be given a hat full of chances in Dortmund and the in form Kevin Volland, as well as Die Werkself's danger men out wide, could prove to be unplayable for Peter Stöger's side.
Prediction: Borussia Dortmund 1-3 Bayer Leverkusen