The acquisition of a motile and invasive phenotype is an important step in the development of tumors and ultimately metastasis. This step requires the abrogation of cell–cell contacts, the remodeling of the extracellular matrix and of cell–matrix interactions, and finally the movement of the cell mediated by the actin cytoskeleton. Evidence for participation of Rho GTPases in migration and invasion is addressed in this review with emphasis on epithelial cells and the contribution of Rho GTPases toward tumor invasion. The Rho GTPases, including Rac, Cdc42, and Rho, have been implicated in the establishment of cell–cell contacts and of cell–matrix interactions crucial to attaining a fully polarized epithelial state, and they are known for their regulation of the actin cytoskeleton and transcriptional activation. Under aberrant conditions, however, they have been implicated in motility, invasion, and some aspects of metastasis. It is well known that Rho GTPases are activated by different classes of transmembrane receptors and that they transmit these signals to their effector proteins. These downstream targets include not only adaptor proteins and kinases which affect the actin cytoskeleton, but also transcription factors leading to expression of genes necessary for the drastic morphological changes which accompany these processes.