In the last decade, several efforts have been made to comprehend the molecular basis of hypertension through the study of Angiotensin II antagonists (AT1 antagonists or class of SARTANs since they share the same suffix in their empirical name). The structural features which determine the pharmacophoric segments of SARTANs are examined using a combination of QSAR and conformational analysis. The final scope of these studies is the prediction of the drug-receptor interactions. Many efforts dedicated to site directed mutagenesis on the human AT1 receptor have identified binding regions for non peptide antagonists. Lack of x-Ray data for the AT1 receptor enforces researchers to use computational methods in order to model it. Recent homology based models of the AT1 receptor have been built on the crystal structure of the bovine rhodopsin. Computer programs dedicated to docking small molecules into protein binding pockets in silico are currently applied. This review article demonstrates the determination of a possible active site of the receptor merging data from biophysical and mutational studies as well as theoretical calculations using SiteID (SYBYL) software. In particular, results show that the site of action for non peptide AT1 antagonists includes aminoacids such as Lys199, Val108 and His256 located at the mesophase of lipid bilayers. Such topography of these key aminoacids has been proposed to be the location of AT1 antagonists using biophysical techniques. The obtained data support the two step mechanism of action proposed in our previous studies. Manual placement of the classic AT1 antagonist, losartan in the pocket using its low energy conformation as determined elsewhere through a combination of NMR and molecular modeling techniques show its suitable fit characterized by energy favored multiple contacts.