Anchorage dependence of growth blocks cell proliferation in inappropriate environments, thereby inhibiting cancer cell invasion and metastasis. Inhibition of growth regulatory pathways, including Rac, Erk and PtdIns 3-kinase in non-adherent cells mediates this effect. Here, we review recent work showing that integrin-mediated adhesion controls Rac binding to membranes. Rac binding sites can be found within cholesterol-enriched membrane domains, which are internalized when cells are deprived of adhesion. Endocytosis of these domains is mediated by caveolae and regulated by caveolin-1 phosphorylated on Tyr 14. This mechanism can account for the control of multiple pathways by integrins, thus providing an important mechanism for anchorage dependence of growth.