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While melanoma is less common than some other skin cancers, it is responsible for nearly 10,000 deaths in the USA each year alone. For many decades, very limited treatment options were available for patients with metastatic melanoma. However, recent breakthroughs have brought new hopes for patients and providers. While targeted therapy with BRAF and MEK inhibitors represents an important cornerstone in the treatment of metastatic melanoma, this chapter carefully reviews the past and current therapy options available, with a significant focus on immunotherapy-based approaches. In addition, we provide an overview of the results of recent advances in the adjuvant setting for patients with resected stage III and stage IV melanoma, as well as in patients with melanoma brain metastases. Finally, we provide a quick overview over the current research efforts in the field of immuno-oncology and melanoma.