A central unresolved issue in modern cell biology concerns how eukaryotic cell migration is achieved. Although the underlying mechanics of cell locomotion appear similar in cells ranging from amoebae to leukocytes, the organisms that have been historically studied have not been amenable to the techniques of modern molecular genetics. The recent development of high-efficiency gene targeting technology for Dictyostelium discoideum, coupled with the classic cell migration behavior of this organism, offers an opportunity to resolve many of the controversial issues concerning cell locomotion.