The renin-angiotensin system plays a critical role in the pathogenesis of several cardiovascular diseases, largely through activation of type I angiotensin (AT(1)) receptors by angiotensin II. Treatment with AT(1) receptor blockers (ARBs) is a proven successful intervention for hypertension and progressive heart and kidney disease. However, the divergent actions of AT(1) receptors on individual cell lineages in hypertension may present novel opportunities to optimize the therapeutic benefits of ARBs. For example, T lymphocytes make important contributions to the induction and progression of various cardiovascular diseases, but new experiments indicate that activation of AT(1) receptors on T cells paradoxically limits inflammation and target organ damage in hypertension. Future studies should illustrate how these discrepant functions of AT(1) receptors in target organs versus mononuclear cells can be exploited for the benefit of patients with recalcitrant hypertension and other cardiovascular diseases.