Cell biologists have long been interested in understanding the machinery that mediates movement of proteins and lipids between intracellular compartments. Much of this traffic is accomplished by vesicles (or other membranous carriers) that bud from one compartment and fuse with another. Given the pivotal roles that large protein complexes play in vesicular trafficking, many recent advances have relied on the combined use of X-ray crystallography and electron microscopy. Here, we discuss integrated structural studies of proteins whose assembly shapes membranes into vesicles and tubules, before turning to the so-called tethering factors that appear to orchestrate vesicle docking and fusion.