Stimulated by hormones and sensory stimuli, serpentine receptors promote the release of GDP that is bound to the alpha subunit of trimeric G proteins and its replacement by GTP. Recent investigations have begun to define the sizes, shapes, and relative orientations of receptors and G proteins, the surfaces through which they interact with one another, and conformational changes in both sets of molecules that underlie receptor-catalyzed guanine-nucleotide exchange.