Calcium antagonists are one of the widely available classes of antihypertensive agents. Their broad appeal is attributable to several features, including their efficacy, their beneficial characteristics such as metabolic neutrality, and the occurrence of relatively few nuisance-type side effects. Despite these attributes, a number of retrospective analyses have suggested that calcium antagonists may be detrimental and may both promote adverse cardiovascular events and increase the risk of cancer by interfering with cellular apoptosis. On the basis of this and other retrospective analyses, Furberg and Psaty (Am J Hypertens 1996; 9: 122-125) have proposed that the use of calcium antagonists as first-line antihypertensive agents should be discontinued. I have previously countered these allegations and have suggested that they are not relevant to the newer calcium antagonist formulations in current use. It is not widely appreciated that different formulations of the same chemical moiety can produce markedly different hemodynamic and neurohormonal effects, due to differences in the rate of drug delivery into the systemic circulation. During chronic treatment with dihydropyridine calcium antagonists, major fluctuations in blood pressure (rapid onset and offset of antihypertensive effects) during the dosing interval may occur for drugs and formulations that are short acting. In contrast, slow-release formulations of otherwise rapidly absorbed dihydropyridines achieve a more gradual and sustained antihypertensive effect. It is probable that newer calcium antagonist formulations that are truly once daily and do not provoke intermittent sympathetic activation or a cardioacceleratory response will not promote adverse cardiovascular events.