This chapter reviews the role of calcium and magnesium in causing and ameliorating brain ischemia, respectively. Three different effects of hypercalcemia are posited to contribute to the development and severity of brain ischemia: (i) hypercalcemia stimulates vascular smooth muscle causing vasoconstriction; (ii) increased calcium concentrations enhance platelet aggregation and activate the body's intrinsic coagulation system; and (iii) calcium entry into cells, a process enhanced by an elevated extracellular-to-intracellular calcium ion gradient, causes cytotoxic effects that promote cell death and brain infarction. The rationale for the use of calcium antagonists in the prevention or treatment of secondary brain ischemia was based on the assumption that these drugs reduce the frequency of vasospasm by counteracting the influx of calcium into vascular smooth muscle cells. There is some benefit from the use of the dihydropyridine CCA nimodipine for improving outcome after aneurysmal subarachnoid hemorrhage.