In addition to the well-known complexities inherent in the recognition of hypomagnesemia and/or magnesium depletion, the management of magnesium deficiency oftentimes is not straightforward and requires the understanding of several important principles. Among these is that the avoidance of ineffective undertreatment of patients with symptomatic severe depletion may require parenteral administration of quite large amounts of magnesium for several days. This point is evident in the included case example describing a patient in whom the small amounts of magnesium given initially were entirely ineffective. The use of the various protocols to provide a patient with magnesium by the parenteral route requires consideration of several factors. The purpose of this paper is to provide the practitioner with a comprehensive, clinically useful review of the oral and parenteral therapy of patients with magnesium depletion.