Magnesium (Mg) deficiency commonly occurs in critical illness and correlates with a higher mortality and worse clinical outcome in the intensive care unit (ICU). Magnesium has been directly implicated in hypokalemia, hypocalcemia, tetany, and dysrhythmia. Moreover, Mg may play a role in acute coronary syndromes, acute cerebral ischemia, and asthma. Magnesium regulates hundreds of enzyme systems. By regulating enzymes controlling intracellular calcium, Mg affects smooth muscle vasoconstriction, important to the underlying pathophysiology of several critical illnesses. The principle causes of Mg deficiency are gastrointestinal and renal losses; however, the diagnosis is difficult to make because of the limitations of serum Mg levels, the most common assessment of Mg status. Magnesium tolerance testing and ionized Mg2+ are alternative laboratory assessments; however, each has its own difficulties in the ICU setting. The use of Mg therapy is supported by clinical trials in the treatment of symptomatic hypomagnesemia and preeclampsia and is recommended for torsade de pointes. Magnesium therapy is not supported in the treatment of acute myocardial infarction and is presently undergoing evaluation for the treatment of severe asthma exacerbation, for the prevention of post-coronary bypass grafting dysrhythmias, and as a neuroprotective agent in acute cerebral ischemia.