The Na+,K+-ATPase, or sodium pump, is well known for its role in ion transport across the plasma membrane of animal cells. It carries out the transport of Na+ ions out of the cell and of K+ ions into the cell and thus maintains electrolyte and fluid balance. In addition to the fundamental ion-pumping function of the Na+,K+-ATPase, recent work has suggested additional roles for Na+,K+-ATPase in signal transduction and biomembrane structure. Several signaling pathways have been found to involve Na+,K+-ATPase, which serves as a docking station for a fast-growing number of protein interaction partners. In this review, we focus on Na+,K+-ATPase as a signal transducer, but also briefly discuss other Na+,K+-ATPase protein–protein interactions, providing a comprehensive overview of the diverse signaling functions ascribed to this well-known enzyme.