G protein signaling pathways regulate heart development and adult cardiac function. G protein activity is controlled by the interplay between receptor-catalyzed activation and the inhibitory regulators of G protein signaling (RGS) proteins. Most RGS proteins are GTPase accelerating proteins (GAPs) for Gi and Gq class G protein alpha subunits, and thereby terminate signaling. However, RGS proteins also provide scaffolding properties to help assemble or maintain signaling complexes. Thus, RGS proteins are kinetic regulators that may sharpen both signal activation and termination. The five subfamilies of mammalian RGS proteins contain a characteristic RGS domain and distinct flanking domains that convey lipid and/or protein interactions within receptor complexes. The RGS domain provides GAP activity and additional interactions with the receptor complex. Distantly related RGS-like (RGL) proteins provide other regulatory and effector functions in G protein signaling pathways. RGS and RGL proteins provide exciting new therapeutic targets to combat cardiovascular diseases.