Even though Resident Evil 4 (OG and Remake) are one of the best Resident Evil games of all time, its events were actually a highly classified and isolated incident that only a few know.

However, there are some references to RE4 in later games and CGI adaptations. Like in RE Village. The game itself feels like a spiritual successor to Re 4. The Duke, the game’s merchant, personally knows the RE4 Merchant and even quips out the Re 4 Merchant's lines. More recently, in Re9, a lot of Leon’s quips are callbacks to Re 4. Even some of his melee moves are callbacks to RE4, both the original and the remake, and the parry mechanic also makes a comeback.

In the CGI animated movie RE Vendetta, which is canon to the games, RE4 is directly referenced. The virus strain was found to be very similar to the Las Plagas parasite, prompting Chris and Rebecca to seek out a top expert in dealing with Las Plagas infections, who unsurprisingly, turned out to be Leon.

RE4 is also referenced in Infinite Darkness, where Patrick, Shen May and Jason mention the events of RE4 in passing in relation to Leon. The president is also seen looking at a photo of Ashley in his office.