The presence, and in many cases the regulated synthesis, of components of the renin-angiotensin system have been demonstrated in multiple tissues, indicating the existence of tissue angiotensin-generating systems. These vary with respect to which renin-angiotensin system components are synthesized locally and which are taken up from plasma. Enzymes unrelated to the classical renin-angiotensin system may also contribute to tissue angiotensin synthesis. However, based on the available data, the prevailing opinion that kidney-derived renin is in all cases the only physiologically relevant renin in tissues must be revised. Also there is evidence indicating a role for tissue angiotensin systems in the pathogenesis of cardiovascular disease and in cardiovascular structural remodeling. The angiotensin-regulated synthesis of aldosterone in cardiac tissue has been described, suggesting the possibility that a renin-angiotensin-aldosterone system exists in the heart. In addition, intracellular (intracrine) sites of angiotensin action have been reported. Some of these findings have implications for therapeutics and, in particular, for the use of angiotensin converting-enzyme inhibitors and angiotensin receptor blockers. Finally, tissue angiotensin systems outside the cardiovascular system also appear to be physiologically relevant.