Acceptance of the notion that physiologically specific interruption of the renin-angiotensin-aldosterone system (RAAS) is of considerable therapeutic benefit in the treatment of hypertension and congestive heart failure has generated great interest in the search for novel pharmacological inhibitors. The RAAS is expressed at the whole body, organ/tissue and cellular level through the action of the octapeptide angiotensin II (Ang II), the primary effector molecule of the RAAS. The availability of selective, potent, orally active and long-acting nonpeptide Ang II type 1 (AT1) receptor antagonists provided the opportunity to obtain the benefits of selectively blocking the RAAS at the level of the AT1 receptor that mediates most, if not all, of the important actions of Ang II, and avoid the nonspecificity of the Ang I converting enzyme (ACE) inhibitors. Losartan was the first, but by no means remained the only nonpeptide AT1 receptor antagonist. Numerous other "sartans" have emerged in the past several years and successfully completed clinical development. With the exception of Eprosartan, all others, i.e. Candesartan, Irbesartan, Saprisartan, Tasosartan, Telmisartan, Valsartan and Zolasartan, are based on modifications of Losartan's prototypic chemical structure. AT1 receptor antagonists represent the newest addition to the arsenal of cardiovascular therapeutics. The predominant role of the AT1 receptor in mediating the pathophysiological role of Ang II underlies the effectiveness of this novel class of agents to lower arterial blood pressure, reduce pre- and afterload, inhibit sympathetic nervous system activity and prevent cardiovascular hypertrophy and cardiac failure induced by inappropriate control of the RAAS.