Affective disorders (depression) are considered as chronic illnesses leading to substantial disability, morbidity and mortality. While the etiology and pathophysiology of these diseases are still poorly recognized, the most important problems concerning them are low treatment response, treatment resistance and/or tolerance and risk of relapse.

Recently published review articles have already demonstrated the important role of zinc in the pathophysiology and treatment of affective disorders, plus discussed the potential value of zinc as a marker of these diseases. This present concise review will update the experimental and clinical data on the antidepressant activity of zinc and focus on the mechanisms of its action. The mechanisms involving NMDA and AMPA glutamate, 5-HT1A serotonin and the GPR39 zinc-sensing receptor and intracellular pathways will be discussed.