Cutaneous melanoma is a malignant neoplasm of melanocytes, with constantly increasing incidence. Risk factors are intermittent exposure to intense solar radiation, the presence of dysplastic and congenital nevi, a positive family history of melanoma, and skin phototypes I and II. Melanoma diagnosis is based on detailed dermatoscopic and physical examination and pathohistological findings. Treatment must be adapted to the stage of the disease, and includes surgical intervention if possible and adjuvant therapy. Systemic adjuvant therapy experienced a real revolution with the development of immunotherapy and targeted therapy and became the standard in the treatment of melanoma. Immunotherapy prevents the inhibition of cellular immunity that allows melanoma cells to evade the immune response. Targeted therapy, on the other hand, blocks cellular mechanisms essential in the proliferation process, thus stopping the growth and multiplication of melanoma cells. Sometimes certain combinations of these two therapies are used and sometimes with systemic chemotherapy. This paper presents the basic therapeutic approaches in the systemic treatment of melanoma and their application in certain stages of the disease.