Summary: The introduction of immunotherapy to the treatment of advanced melanoma was a revolution, and together with targeted therapy with BRAF/MEK inhibitors, it became possible to extend several times the median patients' overall survival. The role of immunotherapy in the first-line treatment of metastatic disease seems to be established. It is also the standard of care for a disease with a high risk of recurrence after surgery, which will be discussed in another chapter of this issue. The chapter below presents the results of clinical studies on the effectiveness of anti-PD and anti-CTLA-4 antibodies in treating patients with metastatic, locally advanced/unresectable melanoma. Also, it discusses the potentially most effective systemic treatment sequence. Available is also research focused on a group of patients with particularly poor prognosis, i.e., with dissemination to the central nervous system. It is essential to apply the principles of diagnosis and treatment of side effects of immunotherapy. Monotherapy immunotherapy is well tolerated, and the rate of severe complications is not high. It is different in the case of a combination of immunotherapy, where a significant percentage of complications occur that require treatment or even its discontinuation. Qualification for treatment requires the attending physician to know the possible complications of treatment and select the appropriate therapy according to the patient's condition, the scope of his cancer, and the presence of accompanying diseases.