Drosophila melanogaster contains a population of blood cells called hemocytes that represent the functional equivalent of vertebrate macrophages. These cells undergo directed migrations to disperse during development and reach sites of tissue damage or altered self. These chemotactic behaviors are controlled by the expression of PDGF/Vegf-related ligands in developing embryos and local production of hydrogen peroxide at wounds. Recent work reveals that many molecules important in vertebrate cell motility, including integrins, formins, Ena/VASP proteins and the SCAR/WAVE complex, have a conserved function in these innate immune cells. The use of this model organism has elucidated how damage signals are activated by calcium signaling during inflammation and that the steroid hormone ecdysone activates immune competence at key developmental stages.