Understanding the physiology of learning and memory is one of the great challenges of neuroscience. The discovery in recent years of long-term potentiation (LTP) of synaptic transmission and the elaboration of the mechanisms involved, in particular the NMDA receptor, offers the prospect not only of improving our understanding of normal memory storage and retrieval, but may also yield insights about various neurological and psychiatric clinical disorders. In this review, we begin by examining the different forms, properties, and methods of inducing LTP, followed by a description of molecular mechanisms thought to underlie the phenomenon. Molecular structure of the receptor is discussed, along with the roles of Ca2+ second messenger systems, synaptic morphology changes, and retrograde messengers in LTP. Finally, implications of the NMDA receptor and LTP in learning, memory, and certain clinical conditions such as epilepsy, Alzheimer's disease, and schizophrenia are discussed.