Inhibition of angiotensin II action or its formation by angiotensin-converting enzyme has been highly successful in the treatment of cardiovascular diseases. Since the identification of chymase as a major angiotensin II-forming enzyme in the human heart and its vessels more than a decade ago, numerous studies have sought to understand the importance of this enzyme in tissue angiotensin II formation and in the pathogenesis of hypertension, congestive heart failure, and vascular disease. Recent studies show that chymase and angiotensin-converting enzyme regulate angiotensin II production in distinct tissue compartments and that, in the pathogenesis of cardiovascular diseases, chymase-dependent effects extend beyond its ability to regulate tissue angiotensin II levels.