Angiotensin-converting enzyme inhibitors have proven to be uniquely effective in inducing regression, or preventing the occurrence, of ventricular hypertrophy associated with systemic hypertension. This has pointed, for many years, to a possible direct involvement of the renin-angiotensin system in the pathogenesis of cardiac hypertrophy. Over the last 10 years further supporting evidence has been forthcoming about direct trophic effects of angiotensin II in several experimental systems. Additionally, we now have rather conclusive evidence for the existence of a local, intracardiac renin-angiotensin system, which is capable of synthesis of all components of the system, and of cleaving, via the classic pathway, angiotensin peptides from the precursor, angiotensinogen. Moreover, a number of studies have demonstrated the capacity of regulatory response and modulation of activity of the local system in response to a variety of pharmacologic perturbations as well as differential expression of specific components under pathologic conditions, including compensatory hypertrophy and remodeling after myocardial infarction, pressure overload hypertrophy, and volume overload hypertrophy. Continued research into the role of the cardiac renin-angiotensin system in the pathogenesis of cardiac hypertrophy and failure will provide us with the tools to devise more specific, targeted strategies for therapeutic intervention or prevention.