The tissue-protective effect of the calcium antagonists is a complex phenomenon that needs to be considered at the cellular as well as the organ level, and with respect to both the vasculature and myocardium. As far as the vasculature and the myocardium are concerned, hypertension is a major risk factor. The dihydropyridine-based calcium antagonists are protective under these circumstances, not only because of their blood pressure-lowering effect but also because of their ability to slow plaque formation and possibly to provide some protection against oxyradical-induced injury. With regard to the myocardium, tissue protection in the presence of hypertension involves not only a reduction in hypertrophy, but also a reduction in ischemia-induced injury and the incidence of damage due to lipid peroxidation.