The prevention and treatment of hypertension remain as major challenges for clinicians all over the world. The recently published Sixth Report of the Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) uses evidence-based medicine in providing guidelines to aid clinicians in the prevention, detection and treatment of high blood pressure, including pharmacological approaches. Calcium antagonists are used widely for the treatment of hypertension, and JNC-VI focuses on specific situations where calcium antagonists could be considered as preferred treatments. There are a large number of calcium antagonists available, with a variety of pharmacodynamic and pharmacokinetic actions. Several sustained-release formulations of these drugs are also available. In terms of blood pressure control, calcium antagonists are more effective as antihypertensive treatments than beta-blockers, ACE inhibitors and angiotensin II receptor blockers in Black patients. The dihydropyridine calcium antagonists have been shown to reduce morbidity and mortality in elderly patients with isolated systolic hypertension. The rate-lowering calcium antagonists can be used as alternatives to beta-blockers in patients with coronary artery disease and hypertension. Calcium antagonists can be used as alternatives to ACE inhibitors in patients with hypertension and concomitant diabetes mellitus and/or renal disease. Some dihydropyridine calcium antagonists may be useful as alternatives to ACE inhibitors in patients with hypertension and systolic heart failure. Calcium antagonists appear to be extremely useful in patients with cyclosporin-induced hypertension, and in patients with hypertension and concomitant Raynaud's phenomenon and/or migraine. The rate-lowering agents can be used in patients with atrial tachyarrhythmias and hypertension. Clinicians should be aware of drug-drug interactions involving calcium antagonists, especially after the recent problems with mibefradil. Although retrospective studies have caused controversy regarding the safety of calcium antagonists in patients with hypertension, recent prospective studies have revealed no major safety concerns with these drugs.