Myosins constitute a superfamily of actin-based molecular motor proteins that mediates a variety of cellular activities including muscle contraction, cell migration, intracellular transport, the formation of membrane projections, cell adhesion, and cell signaling. The 12 myosin classes that are expressed in humans share sequence similarities especially in the N-terminal motor domain; however, their enzymatic activities, regulation, ability to dimerize, binding partners, and cellular functions differ. It is becoming increasingly apparent that defects in myosins are associated with diseases including cardiomyopathies, colitis, glomerulosclerosis, neurological defects, cancer, blindness, and deafness. Here, we review the current state of knowledge regarding myosins and disease.