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This Podcast features an interview with Robert Lefkowitz, corecipient of this year’s Nobel Prize in Chemistry. Lefkowitz has been studying the function of G protein–coupled receptors (GPCRs) for 40 years, and his laboratory has made many important contributions to our current understanding of GPCR structure and function. GPCRs are integral membrane proteins with seven transmembrane–spanning domains. The extracellular portions of the receptors bind to ligands outside the cell, and the intracellular portions of these receptors transduce signaling. GPCRs control many different aspects of cell biology and participate in the regulation of many physiological processes. A large percentage of drugs in use today target GPCRs or their associated signal transduction partners. Lefkowitz discusses GPCR function and specificity, his role in this field of research, and future challenges.