Recent studies of molecular guidance cues including the Slit family of secreted proteins have provided new insights into the mechanisms of cell migration. Initially discovered in the nervous system, Slit functions through its receptor, Roundabout, and an intracellular signal transduction pathway that includes the Abelson kinase, the Enabled protein, GTPase activating proteins and the Rho family of small GTPases. Interestingly, Slit also appears to use Roundabout to control leukocyte chemotaxis, which occurs in contexts different from neuronal migration, suggesting a fundamental conservation of mechanisms guiding the migration of distinct types of somatic cells.