Some of the signaling molecules required for formation of long-term memories are involved primarily in adult brain function, but others participate in a variety of other biological processes. The Notch signaling pathway, which is important for cell fate specification and differentiation in various systems, is also active in the mature brain. Here, we review evidence from recent studies indicating that Notch signaling is required for formation of long-term memories, and discuss possible memory processes modulated by this pathway. We also consider the possible involvement of Notch signaling in cognitive disorders.