S-adenosyl L-methionine (SAMe) is the natural, universal methyl group donor, participating in transmethylation reactions, known and commonly used as a dietary supplement since 1952. It plays an important role in the synthesis of neuromediators and melatonin and mechanisms of epigenetic regulation. The aim of this article is to review the literature about possibilities of SAMe application in the therapy of CNS diseases: depression, dementia syndromes, schizophrenia and somatic disorders. SAMe is the promising dietary supplement, which may be successfully used as a substance increasing effectiveness of the treatment of depression, with antidepressants in monotherapy in mild depressive states or depressive symptoms. SAMe addition to antipsychotic drug, may lead to the improvement of the quality of life and reduction of aggressiveness of patients. SAMe may be an effective substance in the therapy and prophylaxis of mild cognitive impairments and mild dementia syndrome. SAMe possesses some hepatoprotective action, so it may decrease the risk of the development of neoplasm, alcohol-induced liver disease (ALD) and cirrhosis. SAMe improves the functions of joints and decreases the experience of pain in rheumatoid arthritis (RA).