It is well established that leptin is a circulating hormone that is transported into the brain and regulates food intake and body weight via its actions in the hypothalamus. However, leptin receptors are widely expressed in the CNS and several lines of evidence indicate that leptin modulates a variety of neuronal functions. In particular, recent studies have suggested that leptin is a potential cognitive enhancer as it markedly influences the cellular events underlying hippocampal-dependent learning and memory. Indeed, leptin-insensitive rodents display impairments in hippocampal synaptic plasticity and in spatial memory tasks. We have also demonstrated that at the cellular level leptin facilitates the induction of hippocampal long-term potentiation (LTP) via enhancing NMDA receptor function, and that leptin has the ability to evoke a novel form of NMDA receptor- dependent long-term depression. In addition leptin promotes rapid alterations in hippocampal dendritic morphology and synaptic density, which are likely to contribute to the effects of this hormone on excitatory synaptic strength. It is well established that trafficking of AMPA receptors is pivotal for activity-dependent synaptic plasticity, however little is known about the regulation of AMPA receptor trafficking processes by hormonal systems. Our recent studies indicate that leptin rapidly alters the trafficking of AMPA receptors to and away from hippocampal CA1 synapses. The impact of these leptin-driven changes on hippocampal excitatory synaptic function will be discussed.