G-protein-coupled receptors (GPCRs) are the largest group of cell-surface receptors, and represent major molecular targets for drug development. Despite their promise as drug targets, the ascendancy of GPCRs as molecular targets has gradually decreased among newly developed commercially available drugs, in part because conventional screening trials that target the monomers or homodimers have been exhausted. Currently, evidence suggests that many GPCRs associate with other GPCRs to form heterodimers. This association could alter the function of the receptors, yielding a distinct functional unit with novel properties. Therefore, new screening trials such as heterodimer-targeted ligand screening are required to further the drug discovery process. In this issue, Nakamura and colleagues report the development of a novel simultaneous method to monitor dimer formation and signal transduction by GPCRs. This innovation promises to serve as a powerful platform not only for uncovering the novel functions and modes of action of GPCR heterodimerization, but for identifying potential molecular targets for the development of new therapeutic agents as well.