The actin cytoskeleton is affected in many disease states. The mechanisms by which altered structure or expression of actin or of actin-binding proteins cause specific defects are beginning to emerge. Notable recent findings concern the roles in tumor suppression of proteins that link actin to the cell membrane, the specific functions of actin isoforms in cells with a developed contractile apparatus, and the variety of complications caused by release of filamentous actin into extracellular fluids.