In this review, hypotheses are discussed with regard to the role of local, tissue renin-angiotensin systems in the progression of cardiovascular dysfunction. After local renin-angiotensin systems had been described as functionally distinct systems, recent experimental studies have suggested an association between hyperactivity of these local renin-angiotensin systems, and cardiovascular dysfunction. Moreover, the existence of these local renin- angiotensin systems has been confirmed in humans, and early data indicate that the human cardiac renin-angiotensin system may be activated in heart disease. Furthermore, polymorphisms in genes coding for the renin-angiotensin system seem associated with hypertension and left ventricular hypertrophy. These observations may be clinically relevant as inhibition of local renin-angiotensin systems may be an important prerequisite to obtain an optimal clinical effect.