Potassium (K) homeostasis depends on the separate and interrelated regulation of K distribution between the intra- and extra-cellular fluid compartments and adequate renal excretion. This brief review focuses on the regulation of internal K distribution and the renal mechanisms of K handling. Based on clearance, micropuncture, and microperfusion studies, a large body of evidence supports the view that normally, renal secretion of K determines excretion and that the principal tubule cells in the initial and cortical collecting tubule secrete K, whereas K reabsorption may occur in intercalated cells. Studies of the electrochemical driving forces, of intracellular ion activities, the characterization of several ATPases, and patch clamp investigations have provided insight into the role of pumps and channels in those tubule cells that regulate K secretion and reabsorption.