Clinical and experimental evidence indicates alcohol consumption as one of the major causes of magnesium loss from several tissues. As a result of this loss, serum magnesium tends to decrease while urinary magnesium excretion increases 2-3 fold. Experimental data confirm that chronic consumption of 6% ethanol in the Lieber De-Carli diet for 3 weeks results in a marked decrease in total tissue magnesium content in rats. This decrease affects brain, liver and all skeletal muscle, including heart, to a varying extent. While a full picture of the implications of magnesium loss in these tissues is still lacking, it is becoming progressively clear that magnesium loss affects energy production, protein synthesis, cell cycle, and specific functions in the various organs affected. In addition, as magnesium regulated cytokine production and secretion, especially in macrophages and leukocytes, a major role of magnesium deficiency in alcohol-induced inflammatory processes can be envisioned. Considering all these various aspects together, it becomes apparent that magnesium loss may represent a predisposing factor to the onset of alcohol-induced pathologies including brain stroke, sarcopenia, cardiomyopathy, steatohepatitis and cirrhosis. The present review will attempt to clarify some of the mechanisms by which ethanol impairs magnesium transport and homeostasis in brain, brain vasculature, skeletal muscle, heart and liver cells, as a first step towards more mechanistic studies aimed at relating magnesium loss with the incurrence of short- and long-term ethanol-induced complications in these organs.