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The development of brain metastases is a frequent occurrence in patients with disseminated melanoma and contributes to a disproportionate degree of morbidity and mortality. The prognosis is markedly reduced once a patient is diagnosed with central nervous system disease. Definitive therapeutic interventions with resection or stereotactic radiosurgery have improved outcomes and become standard approaches in the management of melanoma brain metastases. With the inclusion of whole-brain radiation in these interventions, there has been a reduction in local recurrences, but no improvement in the overall survival. Still, many patients are not candidates for surgery nor radiotherapy nor develop progressive central nervous system disease after definitive therapy. As new immune-based and targeted therapeutic agents are developed for the treatment of metastatic melanoma, understanding their activity in brain metastases is necessary for effective patient management. In this review, we discuss the biology of brain metastases in metastatic melanoma, current treatment approaches with surgery and radiotherapy, and future systemic therapeutic strategies.