AbstractNitric oxide has pronounced effects on cellular functions normally associated with the cytoskeleton, including cell motility, shape, contraction, and mitosis. Protein S‐nitrosylation, the covalent addition of a NO group to a cysteine sulfur, is a signaling pathway for nitric oxide that acts in parallel to cyclic guanosine monophosphate (cGMP), but is poorly studied compared to the latter. There is growing evidence that S‐nitrosylation of cytoskeletal proteins selectively alters their function. We review that evidence, and find that S‐nitrosylation of cytoskeletal targets has complementary but distinct effects to cyclic‐GMP in motile and contractile cells—promoting cell migration, and biasing muscle contraction toward relaxation. However, the effects of S‐nitrosylation on a host of cytoskeletal proteins and functions remains to be explored.