Quantitative structure-activity relationships of various classes of antihypertensive agents, e.g., sympatholytic agents, diuretics, direct or peripheral vasodilators, potassium channel activators, angiotensin-converting enzyme inhibitors, renin inhibitors and miscellaneous agents (platelet aggregation inhibitors) are reviewed. This review gives an overall picture of the mode of action of each class of drugs and points out their specific physicochemical and structural properties governing their action. For example, in the case of centrally acting drugs (sympatholytic agents) it has surfaced that the prime factors governing their activity are lipophilic and steric properties of the molecules, and at the receptor level a charge-transfer complex is formed between the molecule and the receptor. It is, however, observed that for peripherally acting sympatholytic agents the prime role is played by only lipophilicity. In the case of diuretics, the electronic characters of molecules are found to be more dominant than their lipophilic property, but for direct vasodilators and ACE inhibitors both electronic and lipophilic properties seem to be equally important. In renin or platelet aggregation inhibitors, the structural properties appear to be more important. However, the fundamental property that is overwhelmingly involved in the majority of antihypertensive agents appears to be the lipophilicity, suggesting that in most of the cases the hydrophobic interaction would play the major role in drug action.