Signal transduction mediated by heterotrimeric G proteins that couple to heptahelical receptors requires the involvement of many different proteins. Although some of the early evidence suggested that signal transduction components were assembled into complexes, much of the data supported an alternative hypothesis positing that the process involved transient interactions driven by random collision events. However, recent data indicate that many of the components involved in signal transduction do indeed form complexes. Here we review the evidence for these complexes and how they contribute to the specificity and efficiency of signaling in cells that must manage numerous signal transduction pathways.