Rho signaling pathways in vascular smooth muscle cells are highly activated in hypertension, a condition associated with a variety of vascular diseases, including restenosis injury and atherosclerosis. In this review we suggest that inflammatory cytokines and agonists of G protein-coupled receptors that activate Rho are effective triggers of vascular disease. Accordingly, Rho kinase inhibitors and statins may have therapeutic potential for preventing vascular disease characterized by Rho-mediated cell proliferation and gene expression.