Over the past five years drug therapy of disseminated melanoma took a giant step forward. In clinical practice there are several fundamentally new classes of drugs: inhibitors of the individual components of MAPK-signaling pathway and modulators of a work of immunological synapse (inhibitor of CTLA4 ipilimumab, inhibitors of PD1 nivolyumab and pem- brolizumab).Here are presented features of the mechanism of action of new immunotherapeutic agents, the review of results of their clinical use, the description of the main treatment- related adverse events. The interaction of new approaches with other methods of systemic treatment and an algorithm for per- sonalized use of these methods is regarded. Modern means of therapy allow achieving expressed and long effects giving pos- sibility in some cases to cure a patient. Rational sequential and combined use of different variants of systemic treatment for disseminated melanoma, appropriate diagnosis and treatment of treatment-related adverse events can significantly increase the length and quality of life of patients.