Zinc is an important modulator of glutaminergic transmission. Recent data indicate that pathology of amino-acidergic neurotransmission may contribute to mood disorders and may be involved in antidepressant-like actions in laboratory models. A growing body of evidence implicates a derangement of zinc homeostasis in mood disorders. The zinc deficiency is related to a variety of psychological symptoms especially depression. There are many reports indicating significant changes in blood levels of zinc during a depressive episode. Moreover zinc exhibits antidepressant-like and anxiolytic-like effects in animal models of depression, in rodents. Recent data revealed that zinc enhances the antidepressant effect in laboratory animals. This article reviews the alterations in central and peripheral zinc homeostasis in relation to pathophysiology and treatment of depression.