G protein-coupled receptors (GPCRs) modulate diverse physiological and behavioral signaling pathways by virtue of changes in receptor activation and inactivation states. Functional changes in receptor properties include dynamic interactions with regulatory molecules and trafficking to various cellular compartments at various stages of the life cycle of a GPCR. This review focuses on trafficking of GPCRs to the cell surface, stabilization there, and agonist-regulated turnover. GPCR interactions with a variety of newly revealed partners also are reviewed with the intention of provoking further analysis of the relevance of these interactions in GPCR trafficking, signaling, or both. The disease consequences of mislocalization of GPCRs also are described.