Magnesium is one of the most important elements in the human body and is involved in a number of biochemical processes crucial for the proper functioning of the cardiovascular, alimentary, endocrine, and osteoarticular systems. It also plays a vital modulatory role in brain biochemistry, influencing several neurotransmission pathways associated with the development of depression. Personality changes, including apathy, depression, agitation, confusion, anxiety, and delirium are observed when there is a deficiency of this element. Rodents receiving a diet deficient in magnesium displayed depressive behaviour that was reversed by antidepressant drugs. Poor nutrition, gastrointestinal and renal diseases, insulin resistance and/or type 2 diabetes, alcoholism, stress, and certain medications may lead to magnesium deficiency. Since the extracellular concentration of magnesium ions may not reflect their intracellular level, none of the current methods of evaluating magnesium status is regarded as satisfactory. The mood-improving potential of magnesium compounds have been confirmed by the results of numerous pre-clinical and clinical studies. It seems that magnesium supplementation is well-tolerated and enhances the efficacy of conventional antidepressant treatments, and as such could be a valuable addition to the standard treatments for depression, although differences in bioavailability between inorganic and organic compounds should be taken into consideration.