Although mood disorders such as depression are better diagnosed, their treatment often remains unsatisfactory. Pharmacological treatments of depression mostly target the central monoaminergic systems, especially serotonergic transmission. Various adverse effects (e.g. weight gain, nausea, headache, constipation), the relative inefficiency of the treatments (response rate no more than 50–60%) as well as the delay in the onset of therapeutic action represent some serious limitations. In addition to the improvement of selectivity of molecules available on the market and a better understanding of their mechanisms of action, other neurotransmitter systems that have received little attention so far are now being targeted for the treatment of depression. Glutamate receptor antagonists (e.g. ketamine, traxoprodil), nicotinic modulators (e.g. mecamylamine, varenicline), atypical antipsychotics (e.g. aripiprazole, quetiapine) possess antidepressant activity. The focus of the proposed research is to review recent developments in this field and the new prospects that it opens.