The Island is the third and last major area seen in Resident Evil 4. After defeating Ramon Salazar, Leon S. Kennedy gets a ride to the island where Ashley is held from Ada. Before being defiled by Saddler and Los Iluminados, the Island was what appeared to be a private military island off the coast of Spain. It featured several bases, including a top-secret research facility. It also had a hospital, a prison, a communications tower, and a ruins complex within its inner walls. The island is home to some of the most powerful and most fearsome enemies in the game. The island and it's culture may have had some ties to the Los Iluminados for centuries, if not millennia prior to the events of the game, as imagery for the Island and to some degree its mythological figures of a jaguar, eagle, and serpent were utilized by the cult.
The Island is reached at Chapter 5-1 and continues until the Final Chapter. Common enemies here are Saddler's private Militia, armed with maces, shields, axes, crossbows, and stun rods. The sub-bosses include Gatling Man; the Regenerador and Iron Maiden. The bosses are U3, Jack Krauser and Osmund Saddler himself.
- During the Castle stage, some cultists will say "No dejes que escapen a la isla vivo," which means "Do not let them escape to the island alive", revealing the next scenario in Leon's mission to rescue Ashley.