A common property of cell signaling systems is the ability to adapt to chronic stimulation. A genetic analysis of receptor/G protein signaling in yeast has led to the identification of a new class of regulators of G protein signaling (RGS proteins), as well as to new insights about the regulatory role of G protein modifications (myristoylation, palmitoylation). Similar modes of regulation are now known to exist in humans. These discoveries fill some important gaps in our understanding of signal transduction, and provide an instructive example of how model organisms, like yeast, can provide new insights relevant to signal regulation in higher eukaryotes.