The role of magnesium (Mg) in the prevention of ischemia-induced injury during cardioplegic arrest and in the treatment of cardiac arrhythmias has been considered. Although Mg possesses negative inotropic properties, potassium (K) is more effective than Mg in inducing cardiac arrest. The rationale for the inclusion of Mg in cardioplegic solutions therefore lies not in its cardioplegic properties, but in its ability to influence other cellular events such as the loss of Mg and K and perhaps to counter the detrimental effects of ischemia by antagonizing calcium (Ca) overload. Most of the Mg in the cardiac cell is complexed with high energy phosphate compounds and the loss of Mg during ischemia may restrict the repletion of ATP upon reperfusion and so impair the return of normal contractile function. The ability of Mg to limit K efflux from the cell is of importance not only in the prevention of ischemia-induced K loss but also in the treatment of digitalis-induced arrhythmias. Elevation of extracellular Mg has been shown to reduce the intracellular sodium ion activity ([Na]i) and this decline in [Na]i can be related to the negative inotropic properties of Mg. Mg may therefore exert some of its antiarrhythmic and antiischemic effects by limiting [Na]i-stimulated Ca influx (or facilitating Ca efflux) and hence preventing cellular Ca overload.