Tethers are a diverse group of loosely related proteins and protein complexes grouped into three families based on structural and functional similarities. A well-accepted role for tethering factors is the initial attachment of transport carriers to acceptor membranes prior to fusion. However, accumulating evidence indicates that tethers are more than static bridges. Tethers have been shown to interact with components of the fusion machinery and with components involved in vesicle formation. Tethers belonging to the three families act at the same stage of traffic, suggesting that they mediate distinct events during vesicle tethering. Thus, multiple tether-facilitated events are required to provide selectivity to vesicle fusion. In this review, we highlight findings that support this model. © 2009 Federation of European Biochemical Societies.