As the cellular and molecular mechanisms of major arterial diseases such as atherosclerosis and hypertension are being more clearly defined, it is becoming apparent that these pathological processes share a number of functional and biochemical features in the vessel wall. Typically, arterial diseases are associated with functional and structural wall alterations including modified contractile properties, smooth muscle cell hypertrophy and proliferation, endothelial dysfunction, excessive extracellular matrix accumulation and inflammation. Small G proteins of the Rho family are defined as major regulators of cell functions including migration, proliferation, differentiation and gene transcription. Recent studies have demonstrated that activation of Rho proteins appears to be a common component for the pathogenesis of hypertension and vascular proliferative disorders. Functional analyses have further revealed that RhoA-dependent pathways are involved in excessive contraction, migration and proliferation associated with arterial diseases. This review focuses on the role of Rho proteins, in particular RhoA, in vascular smooth muscle cells and the involvement of Rho-dependent signaling pathways in vascular diseases.