Attention is growing for a potential role of magnesium in the pathoetiology of cardiovascular disease. Magnesium modulates mechanical, electrical and structural functions of cardiac and vascular cells, and small changes in extracellular magnesium levels and/or intracellular free magnesium concentration may have significant effects on cardiac excitability and on vascular tone, contractility and reactivity. Thus, magnesium may be important in the physiological regulation of blood pressure whereas alterations in cellular magnesium metabolism could contribute to the pathogenesis of blood pressure elevation. Although most epidemiological and experimental studies support a pathological role for magnesium in the etiology and development of hypertension, data from clinical studies have been less convincing. Furthermore, the therapeutic value of magnesium in the management of essential hypertension is unclear. The present review discusses the molecular, biochemical, physiological and pharmacological roles of magnesium in the regulation of vascular function and blood pressure and introduces novel concepts relating to magnesium as a second messenger in intracellular signaling in cardiovascular cells. In addition, alterations in magnesium regulation in experimental and clinical hypertension and the potential antihypertensive therapeutic effects of magnesium are addressed.