Myosins are a large family of actin-based cytoskeletal motors that use energy derived from ATP hydrolysis to generate movement and force. Myosins of classes II, V and VI have specific pre- and postsynaptic roles that are required for synapse function. They also facilitate several forms of synaptic plasticity. Interestingly, the myosins of these classes differ markedly in important aspects of their molecular mechanisms of function. Accordingly, their major roles at synapses are diverse and include the regulation of actin cytoskeleton dynamics in dendritic spines and powering of synaptic cargo transport.