A number of studies in experimental animal models have demonstrated the potential direct antiatherosclerotic effects of calcium antagonists. This class of compounds can influence several processes that are involved in the development of atherosclerotic lesions. This action is independent of either blood pressure reduction or hypercholesterolemia. A major problem encountered from the experimental data are the high doses used, which are several times higher than those used in the treatment of humans. One notable exception to this problem is the second-generation calcium antagonist isradipine, which exerts a direct antiatherosclerotic effect in rabbits at doses similar to those used in the clinic. Thus, this review is a summary of the effects and mechanisms of the antiatherosclerotic activity of isradipine.