Protein kinases and phosphatases are intimately involved in several forms of synaptic plasticity. They play a critical role in the initiation of long-term potentiation and long-term depression, as well as in the induction of genes that permit long-term expression of altered synaptic states. Recent findings demonstrate a central role for the cAMP signaling pathway in the persistent phase of long-term potentiation. Genetic approaches have established that the transcription factor CREB is essential for long-term memory.