The heterotrimeric G proteins are extensively involved in the regulation of cells by extracellular signals. The receptors that control them are often the targets of drugs. There are many isoforms of each of the three subunits that make up these proteins. Thus far, genes for at least sixteen alpha subunits, five beta subunits, and eleven gamma subunits have been identified. In addition, some of these proteins have splice variants or are differentially modified. Based upon what is already known, there are well over a thousand possible G protein heterotrimer combinations. The role of subunit diversity in heterotrimer formation and its effect on signaling by G proteins are still not well understood. However, many current lines of research are leading toward an understanding of these roles. The functional significance of subunit heterogeneity is related to the mechanisms used by G proteins to transmit and integrate the many signals coming into cells through this system. Described here are the basic mechanisms by which G proteins integrate cellular responses, the possible role of subunit heterogeneity in these mechanisms, and the evidence for and against their physiological significance. Recent studies suggest the likely possibility that subunit heterogeneity plays an important role in signaling by G proteins. This role has the potential to extend substantially the flexibility of G proteins in mediating cellular responses to extracellular signals. However, the details of this are yet to be worked out, and they are the subject of many different avenues of research.