Twice the two teams have met this season, once in the Bundesliga and again in the DFB-Pokal, and each time the Wolves have emerged triumphant.
"Both defeats hurt us and we desperately want to get our own back," said midfielder Gonzalo Castro.
Leverkusen's home form against Wolfsburg augurs well for that sought-after victory.
The Lower Saxony side have never triumphed at the BayArena in 15 attempts in the top flight of German football, a record Leverkusen's joint-coach Sami Hyypia hopes to maintain on Saturday.
"We've got to show our strength at home and we need these three points to cling on at the top," he said on the club's website.
Leverkusen have a six-point cushion over fourth-placed Schalke and Eintracht Frankfurt in the race for an automatic qualification for the Champions League next season.
Wolfsburg are not entirely out of the running for European football yet either, though, and three points would allow them to throw their hat into the ring once again.
"The games that remain are the most important of them all," said director of sport Klaus Allofs.
"We need to lay the foundations for the future and we want every player to convince us that they belong at this club.
"Every individual has got to show what they can do to help this team in the long term.
"The chance of obtaining a better league position is still there and we should chase it vehemently until the very last second."
The Wolves are without the injured Vieirinha, while Marcel Schafer faces a late fitness test.
Hyypia has a full squad to choose from with the exception of the long-term absentees Karim Bellarabi and Omer Toprak.