GPCRs, the largest family of cell surface signaling proteins and the targets for >30% of FDA-approved drugs, play key physiological and pathophysiological roles, in part through their activation of heterotrimeric G proteins. Recent analyses of human cancer genomes revealed an unanticipated high frequency of mutations in G proteins and GPCRs in many tumor types, including the discovery of mutant GPCRs and G proteins as driver oncogenes. GPCRs also regulate tumor-induced angiogenesis, cancer stem cell maintenance, metastasis, and immune evasion of cancer. Speakers in this symposium will describe efforts to translate such recent knowledge into new pharmacological interventions for cancer prevention and treatment.