In eukaryotes, membrane fusion generally involves Rab-GTPase–dependent tethering of the transport vesicle to the SNARE fusion apparatus at the target membrane. GTP-activated Rab GTPases are associated with vesicle or organelle membranes and bind tethering factors to promote SNARE-mediated vesicle fusion. In the endosomal membrane system, some multisubunit tethering complexes (MTCs), such as the conserved homotypic fusion and vacuole protein sorting (HOPS) complex bind to both Rab GTPases and SNAREs. HOPS comprises six subunits: Vps11, Vps16, Vps18, the SNARE-binding Vps33, and Vps41 and Vps39, which both bind the Rab GTPase Ypt7. Raunser, Ungermann and colleagues have determined the structure of the HOPS complex, using EM, giving the first structural view of a Rab-binding MTC. HOPS has a seahorse-like shape with flexible head and tail regions. 3D reconstructions of HOPS subcomplexes and antibody labeling were used to orient the subunits within the HOPS structure. Vps39-Vps11 occupy the bulky tail, and Vps18 forms the rigid backbone connecting head and tail regions. The side of the head is formed by Vps16-Vps33. Surprisingly, Vps41 was localized to the remainder of the head region, far from Vps39. Nanogold labeling confirmed the presence of two Ypt7 binding sites at opposite ends of the HOPS complex. The authors propose that HOPS is initially recruited to late endosomes through Ypt7 binding to Vps39 and Vps41. A reorientation step may occur so that HOPS can associate with phosphoinositides and the highly curved endosomal surface. This would require Vps39 to release endosomal Ypt7, allowing it to interact with Ypt7 on the vacuole membrane and bringing the membranes closer together to allow Vps33 to promote SNARE assembly. (Proc. Natl. Acad. Sci. USA 109, 1991–1996, 2012)