The neurotransmitter theories of the pathogenesis and treatment of mood disorders presented so far focused mainly on serotonergic and catecholaminergic (noradrenergic and dopaminergic) transmission. In recent decades the attention has been also directed towards a role in the pathogenesis of mood disorders of stress axis dysregulation and of neuroplasticity disturbances, which involve the glutamatergic system. In this paper, a role of glutamatergic neurotransmission in the pathogenesis and treatment of unipolar and bipolar affective illness is presented. In the first part, a role of glutamatergic neurotransmission in the central nervous system is presented, with special focus on glutamatergic receptors. The results of molecular-genetic studies pointing to an association between glutamatergic system genes and a predisposition to unipolar and bipolar affective illness are discussed. In the next part, a summary of neurobiological, including neuroimaging findings as to changes in glutamatergic system in mood disorders is done. Following this, a role of glutamatergic system in the mechanism of action of antidepressant and mood-stabilizing drugs as well as therapeutic activity of drugs modifying glutamatergic system is reviewed. Glutamatergic conception of mood disorders allows for a new look on the pathogenesis and treatment of unipolar and bipolar affective illness.