Functional and structural neuronal plasticity are mediated by a complex network of biochemical signal transduction pathways that control the strength of specific synapses and the formation of new synapses de novo. The neuronal protein kinase Cdk5 has been implicated as being involved in numerous aspects of both functional and structural plasticity through its regulation of signal transduction pathways. In this review the findings of a number of studies are summarized that have advanced our understanding of how Cdk5 may be involved in these processes. We focus on the modulation of protein phosphatase activity in both the hippocampus and basal ganglia, and review findings that indicate Cdk5 is likely to regulate neuronal plasticity in these brain regions. Studies showing involvement of Cdk5 in reward and motor-based plasticity, which are thought to underlie drug abuse, are discussed. Copyright © 2003 S. Karger AG, Basel.