The family members of small Rho-like GTPases, RhoA, Rac1 and Cdc42Hs, are regulators of diverse cellular signalling pathways, including cytoskeletal organisation, transcription and cell–cycle progression. Recent research has given insight into the complex regulation of cell–cell adhesion and migratory responses of epithelial cells. The Rho-like GTPases RhoA, Rac1 and Cdc42Hs as major determinants of cytoskeletal organisation have been identified as key regulators of epithelial architecture, as well as of cell migration. These findings highlight the complex regulation and crosstalk of GTPase-dependent signalling pathways arising from cell–cell and cell–matrix interactions. The molecular mechanism of how Rho-like GTPases couple to molecules mediating either cell–cell adhesion or cell migration will be of particular interest to understand the invasive phenotype of epithelial tumours.