In recent years, an increasing evidence has been accumulated pointing on a role of glutamatergic system in the pathogenesis of mood disorders and in the mechanism of action of antidepressants and mood-stabilizing drugs. In the beginning of this paper, the elements of glutamatergic system were described and the results of molecular-genetic studies on the association of glutamatergic system genes with a predisposition to affective illness, unipolar and bipolar. Next, a role of glutaminergic receptors, mainly NMDA and AMPA, as well as the processes of glutamate release and transport in the mechanisms of antidepressants and mood-stabilizing drugs was presented. The one of the most important mechanism of antidepressant action is reduction of the expression and function of glutamatergic receptor NMDA. In recent decade an evidence has been obtained for a rapid antidepressant effect connected with the influencing glutamatergic system by single infusion of NMDA antagonist receptor, ketamine. Besides of ketamine, data are provided concerning a possibility of antidepressant action for other substances influencing glutamatergic system such as D-cycloserine, amantadine, memantine, traxoprodil, riluzole as well as zinc and magnesium ions. Further elucidation of a role of glutamatergic system in the mechanisms of antidepressants and mood-stabilizing drugs may provide new therapeutic perspectives in mood disorders.