The melastatin (M) transient receptor potential (TRP) channel TRPM4 is selective for monovalent cations and is activated by high levels of intracellular Ca²⁺. TRPM4 is broadly distributed and may be involved in numerous functions, including electrical conduction in the heart, respiratory rhythm, immune response, and secretion of insulin by pancreatic β-cells. The significance of TRPM4 in smooth muscle cell function is reviewed here. Several studies indicate that TRPM4 channels are critically important for pressure-induced cerebral arterial myocyte depolarization and myogenic vasoconstriction as well as autoregulation of cerebral blood flow. Regulation of TRPM4 activity in arterial smooth muscle cells is complex and involves release of Ca²⁺ from the sarcoplasmic reticulum through inositol 1,4,5-trisphosphate receptors and translocation of TRPM4 channels to the plasma membrane in response to protein kinase Cδ. TRPM4 is also present in colonic, urinary bladder, aortic, interlobar pulmonary and renal artery, airway, and corpus cavernosum smooth muscle cells, but its significance and regulation in these tissues is less well characterized.