The role of the actin cytoskeleton in the function of eukaryotic cells is ubiquitous. Regulation of actin polymerization allows cells to control their shape, to move, divide, secrete, and phagocytose. Actin filaments provide strength, connections to other cells and the extracellular matrix, paths for intracellular transport and a scaffold for generating force. Recently, a number of signal transduction pathways have been identified that regulate actin polymerization and contractility. GTP-binding proteins, protein kinases, phosphoinositide kinases, and protein phosphatases all play important roles in determining the location and extent of actin polymerization and contractility of actin/myosin filaments. These pathways allow cells to respond to extracellular signals to regulate movement, the tone of vascular smooth muscle cells, secretion, and phagocytosis. Some pathogens use signal transduction pathways that regulate actin polymerization to invade cells. The signal transduction pathways that regulate actin-dependent events are the focus of this review.