The major impact of calcium-antagonists in prevention strategies of cardiovascular disease evolves from their modulation of signal transduction and metabolic processes controlled by calcium-ions as "second messenger" in cells participating in the early development of vascular atherosclerotic lesions, namely endothelial cells, vascular smooth muscle cells, monocytes/macrophages, T-lymphocytes and platelets. In accordance with experimental data suppression of angiographically early coronary lesions was documented in four independent clinical studies using quantitative analysis of repeated coronary angiography: Nifedipine and Nicardipine reduce angiographically "new" (minimal) lesions to 30-70%, in some cases already after 1 year of treatment. This anti-atherosclerotic effect is independent of known risk factors and indicates a new strategy in "primary" prevention of atherosclerotic vascular disease. In pre-infarction-syndromes calcium-antagonists demonstrate a tendency in attenuating anginal symptoms and progression into definitive infarction. Analysis of studies in acute infarction showed a neutral effect of calcium-antagonists with unchanged infarct-size, regional and global ventricular function or early mortality. In post-infarction patients only strict selection criteria (up to 60% of patients) as well as delayed onset of therapy (> 7 days after infarction) reduce the number of re-infarction and mortality. Subgroup analysis indicate that calcium antagonists with mild afterload reduction and minimal negative inotropic impact might be preferable. The suppression of "early" lesions should be regarded as the predominant benefit for future strategies in prevention of cardiovascular disease with calcium-antagonists.