Membrane fusion within the eukaryotic endomembrane system depends on the initial recognition of vesicles by multisubunit tethering complexes by Rab GTPases and subsequent coupling to SNARE-mediated fusion. The vacuolar HOPS complex combines SNARE and Rab-binding in one complex. Here, I will present insights into the molecular organization of the HOPS complex using a combination of biochemical assays and molecular genetics and structural approaches. Our data provide the foundation to understand the molecular mechanism of a tethering complex in membrane fusion.