Trafficking of cargo molecules through the secretory pathway relies on packaging and delivery of membrane vesicles. These vesicles, laden with cargo, carry integral membrane proteins that can determine with which target membrane the vesicle might productively fuse. The membrane fusion process is highly conserved in all eukaryotes and the central components driving membrane fusion events involved in vesicle delivery to target membranes are a set of integral membrane proteins called SNAREs. The yeast Saccharomyces cerevisiae has served as an extremely useful model for characterizing components of membrane fusion through genetics, biochemistry and bioinformatics, and it is now likely that the complete set of SNAREs is at hand. Here, we present the details from the searches for SNAREs, summarize the domain structures of the complete set, review what is known about localization of SNAREs to discrete membranes, and highlight some of the surprises that have come from the search.