Stroke is a major cause of death and disability, and its prevalence is expected to rise as the population continues to age. Most strokes can be prevented through risk-factor modification and application of effective preventive therapies. Although treatment of dyslipidemia, control of diabetes mellitus, smoking cessation and treatment of atrial fibrillation contribute substantially to stroke prevention, hypertension control remains the single most important intervention. Control of hypertension with diuretics, beta-blockers, inhibitors of the renin-angiotensin system and calcium channel blockers can reduce the risk of first and recurrent stroke. Although blood pressure normalization seems to be the main mechanism for stroke prevention, specific drug effects may also contribute. Findings from recent clinical studies and meta-analyses suggest that calcium channel blockers may have an advantage in stroke prevention. Mechanisms for this greater efficacy may include more effective blood pressure reduction and possibly antiatherosclerotic actions observed with dihydropyridines. The objective of this paper is to discuss effective interventions for optimal stroke prevention, with an emphasis on effective antihypertensive and lipid lowering therapy.