The ability to learn from feedback is a key component of adaptive behavior. This type of learning is traditionally thought to depend on neural substrates in the striatum and not on the medial temporal lobe (MTL). Here we show that in humans the MTL becomes necessary for feedback-based learning when feedback is delayed. Specifically, amnesic patients with MTL damage were impaired at probabilistic learning of cue–outcome associations when response-contingent feedback was delayed by a few seconds, but not when feedback was immediate. By contrast, patients with striatal dysfunction due to Parkinson's disease demonstrated the opposite pattern: impaired learning when trial-by-trial feedback was immediate but not when feedback was delayed, indicating that the striatum is necessary for learning only when feedback is immediate. Together, these results reveal that multiple complementary learning processes support what appears to be identical behavior in healthy individuals and point to an important role for the MTL in feedback-driven learning.