Fusion of Golgi-derived COP (coat protein)-I vesicles with the endoplasmic reticulum (ER) is initiated by specific tethering complexes: the Dsl1 (depends on SLY1-20) complex in yeast and the syntaxin 18 complex in mammalian cells. Both tethering complexes are firmly associated with soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) at the ER. The structure of the Dsl1 tethering complex has been determined recently. The complex seems to be designed to expose an unstructured domain of Dsl1p at its top, which is required to capture vesicles. The subunit composition and the interactions within the equivalent mammalian complex are similar. Interestingly, some of the mammalian counterparts have additional functions during mitosis in animal cells. Zw10, the metazoan homolog of Dsl1p, is an important component of a complex that monitors the correct tethering of microtubules to kinetochores during cell division. This review brings together evidence to suggest that there could be common mechanisms behind these different activities, giving clues as to how they might have evolved.