Experiments with cell lines have unveiled the implication of the Rho/Rac family of GTPases in cytoskeletal organization, mitogenesis, and cell migration. However, there have not been adequate animal models to investigate the role of these proteins in more physiological settings. This scenario has changed recently in the case of the T‐cell lineage after the generation of animal models for Rho/Rac family members, their regulators, and effectors. These studies have revealed the implication of these GTPases on multiple regulatory layers of T‐cells, (...) including the coordination of cytoskeletal change, activation of kinase cascades, stimulation of calcium fluxes, and the induction of gene expression. These pathways affect the transition of different T‐cell maturation stages, the positive/negative selection of thymocytes, T‐cell responses to antigens, and the homeostasis of peripheral T‐lymphocytes. Moreover, these animals have revealed interesting cross‐talks between Rho/Rac pathways and other signal transduction routes that participate in lymphocyte responses. BioEssays 24:602–612, 2002. © 2002 Wiley Periodicals, Inc. (shrink)