Coiled-coil and multisubunit tethers have emerged as key regulators of membrane traffic and organellar architecture. The restricted subcellular localization of tethers and their ability to interact with Rabs and soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) suggests that tethers participate in determining the specificity of membrane fusion. An accepted model of tether function considers them molecular "bridges" that link opposing membranes before SNARE pairing. This model has been extended by findings in various experimental systems, suggesting that tethers may have other functions. Recent reports implicate tethers in the assembly of SNARE complexes, cargo selection and transit, cytoskeletal events, and localized attachment of regulatory proteins. A concept of tethers as scaffolding machines that recruit protein components involved in varied cellular responses is emerging. In this model, tethers function as integration switches that simultaneously transmit information to coordinate distinct processes required for membrane traffic. Copyright © 2006 the American Physiological Society.