Much regarding the engagement of the G(12) family of heterotrimeric G proteins (G(12) and G(13)) by agonist-activated receptors remains unclear. For example, the identity of receptors that couple unequivocally to G(12) and G(13) and how signals are allocated among these and other G proteins remain open questions. Part of the problem in understanding signaling through G(12) and G(13) is that the activation of these G proteins is rarely demonstrated directly and is instead presumed usually from far removed downstream events. Furthermore, receptors that couple to G(12) and G(13) invariably couple to additional G proteins, and thus few events can be linked unambiguously to one G protein or another. In this article, we document receptors that reportedly couple to G(12), G(13) or both G(12) and G(13), evaluate the methodology used to understand the coupling of these receptors, and discuss the ability of these receptors to couple also to G(q).