Our understanding of the molecular mechanisms of membrane trafficking advanced at a rapid rate during the 1990s. As one of the initial protein components of the trafficking machinery to be identified, N-ethylmaleimide sensitive factor (NSF) has served as a reference point in many of these recent studies. This hexameric ATPase is essential for most of the membrane-trafficking events in a cell. Initially, due to its ATPase activity, NSF was thought to be the motor that drove membrane fusion. Subsequent studies have shown that NSF actually plays the role of a chaperone by activating SNAP receptor proteins (SNAREs) so that they can participate in membrane fusion. In this review we will examine the initial characterization of NSF, its role in membrane fusion events, and what new structural information can tell us about NSF's mechanism of action.