It has become apparent in recent years that the cytoskeleton and its associated proteins play a major role in secretion. This review summarizes recent findings on the cytoskeleton organization and the molecular topology of its regulatory proteins, as well as the dynamic changes that occur in this organelle during secretion from neurons and secretory cells. Although two apparently different ultrastructures and molecular organizations of the cytoskeleton seem to be involved in neuronal and secretory cell secretion, there are similarities between the two systems. In both neurons and secretory cells, Ca2+ plays a pivotal role in the control of cytoskeleton dynamics, especially in the changes in actin filament networks observed during secretion.