Angiotensin II (Ang II), an important peptide in cardiovascular physiology, is the product of enzymatic processing of angiotensinogen which involves two proteolytic steps carried out by renin and angiotensin converting enzyme (ACE) sequentially. This system, which plays an important role in cardiorenal homeostasis, is conventionally considered an endocrine system. Increasing evidence supports the existence of this biochemical cascade in many tissues, in addition to its presence in the circulation. The molecular demonstration of tissue renin and angiotensinogen gene expressions suggest that the presence of this system is due, at least in part, to local synthesis. These observations have led to the hypothesis that locally generated angiotensin may be important in the regulation of individual tissue function, in addition to its circulating counterpart. This emerging concept may be important in providing an additional understanding of the role of renin angiotensin in cardiovascular physiology and in the response to pharmacological inhibitors of this system.