Calcium Entry Blockers (CEBs) are a new class of drugs which have been pushing back the frontiers of science and medicine for almost two decades. This report reviews some of the wealth of chemical, biological and clinical data describing the discovery and development of these compounds. The scientific importance, therapeutic benefit and marketing potential of these compounds have caused an explosion of scientific literature describing their effects in many preclinical and clinical settings. The definitional characteristics of these compounds suggest a certain predictability of their biological profile but their therapeutic usefulness varies widely dependent upon their physical properties, net hemodynamic effects, duration of action and incidence of side effects. CEBs appear uniquely suited to the treatment of the underlying complexity of cardiovascular disease. The CEBs of the future may live up to the expectations of pathophysiologically based therapeutics and allow the heart and blood vessels to outlive the cells which they support. The development of CEBs is an evolving story of epic proportions and represents the cooperative efforts of individuals in all areas of science.