Introduction: The incidence of melanoma has increased fivefold during the past three decades. Melanoma can no longer be classified as rare; rather, it is now one of the more frequent tumors. Methods: Recommendations for the diagnosis and treatment of melanoma are laid out in the interdisciplinary S2 guidelines of the German Cancer Society, upon which the present review is based. The goal of this article is to present the clinical core recommendations for treatment in all disease stages. Results: The operative management of primary melanoma usually takes place in two steps. A complete excisional biopsy with a safety margin of about 2 mm is performed in order to establish the histopathological diagnosis. Definitive surgical excision is performed with a safety margin of 1 cm in tumors up to 2 mm thick, 2 cm in thicker tumors. In tumors more than 1 mm thick, sentinel lymph node biopsy should be performed to aid in tumor staging. Radiotherapy is indicated in inoperable tumors of all stages. Adjuvant immunotherapy with interferon-α is recommended in tumors of thickness ≥ 2 mm and in locoregional metastasis. If distant metastasis is present and R0 surgery is not an option, the treatment should primarily comprise monochemotherapy or alternatively the patient should be enrolled in a clinical trial. Conclusion: The recommendations presented here are based predominantly on the results of prospective randomized trials.