The history of introducing antidepressant drugs into psychiatry has been up to 1990. associated mainly with agents acting in various way on serotonergic or/and noradrenergic neurotransmission. The process of recognizing novel pathogenic mechanisms of depression brought up an attention to a role of another neurotransmitters, the disturbances of stress system, as well as to abnormal neuroplasticity processes with a possibility of the therapeutic action of antidepressant drugs via these phenomena. In recent years, the interest has been raised for a concept of treatment of depression by means of regulation of disturbed biological rhythms in this illness. Sleep disturbances occurring in a vast majority of patients make the main clinical manifestation of disturbed circadian rhythms in depression, along with such biochemical abnormalities as altered secretion profiles of many hormones (cortisol, prolactin, thyreotropin and melatonin). These abnormalities may reflect dysfunction of “the biological clock” which main structure is bilateral suprachiasmatic nucleus (SCN). The regulation of SCN activity connected with lighting rhythms is performed mainly by melatonin, acting on M1 and M2 receptors in this brain structure and serotonin pathways from raphe nuclei. In recent years, the antidepressant efficacy of agomelatine has been evaluated, the drug with agonistic action on melatonergic receptors M1 and M2 and antagonistic on serotonergic receptors, type 5HT2C. It has been demonstrated that agomelatine makes an efficacious antidepressant drug with good tolerability. A conspicuous feature of agomelatine is a rapid regulation of sleep disturbances and its lack of effect on sexual functions. The evidence for antidepressant action of agomelatine can make a confirmation for the role of melatonergic system in the pathogenesis and treatment of depression.