Neutrophils and Dictyostelium discoideum share the ability to migrate directionally in response to external chemoattractant gradients. The binding of chemoattractants to specific receptors that are coupled to heterotrimeric G proteins leads to a wide range of biochemical responses that become highly localized as cells polarize and migrate by chemotaxis. The signaling mechanisms that lead to the predominant polymerization of F-actin at the front of cells for propulsion and to myosin II assembly at the sides to suppress lateral pseudopod formation and at the back for retraction are now beginning to emerge.