Abstract: Yeast assays for G-protein-coupled receptors have many attractions due to their simplicity, low cost, and lack of endogenous receptors. Since the first report of functional coupling of the human beta 2 adrenergic receptor to the yeast pheromone-response pathway in 1990, the technology has developed to a point at which more than 30 heterologous GPCRs are now published to couple. Major breakthroughs have come from an understanding of receptor-G protein interactions, alongside advances in knowledge of the structure of heterotrimeric G proteins. Yeast screens have been used to identify ligands both from compound collections and through the autocrine expression of peptide libraries. Yeast genetics has also been applied to a functional analysis of GPCRs and peptide ligands. In this review we describe the historical development of yeast GPCR assay systems and their current applications.