A large body of work on Drosophila melanogaster has identified and characterized a number of key polarity regulators, many of which are required for the regulation of multiple other processes including proliferation, migration, invasion, and tumorigenesis. Humans possess either single or multiple homologues of each of the Drosophila polarity proteins, and in most cases, these are highly conserved between species, implying an important and conserved function for each of the polarity complexes. Recent studies in cultured mammalian epithelial cells have shed some light on the requirement for the polarity complexes in the regulation of epithelial cell function, including an unexpected link to the regulation of directed cell migration. However, many questions still remain regarding the molecular mechanisms of polarity regulation and whether disruption of polarity protein function is an important step in the development of human cancers. Here we will review what is currently understood about the regulation of cell polarity, migration, and invasion and the level of functional conservation between Drosophila and mammalian tissues. Particular reference will be made as to how the Scribble and Par polarity complexes may be involved in the regulation of apical-basal polarity, migration, and tumorigenesis.