Melanoma is the third most common skin malignancy but is the one with the highest propensity to metastasize, potentially able to disseminate to any organ. Spreading to the central nervous system has been historically regarded as an ominous event due to the poor prognosis of the affected patients. Magnetic resonance is fundamental for screening and diagnosis, although histological analysis remains invaluable. Management relies on a multidisciplinary discussion between oncologists, neurosurgeons, and radiologists. Recent trials with dual checkpoint inhibitors have expanded the panorama of treatment options for these patients and are contributing to reshape our conception and approach. With a growing number of immunotherapy agents and small molecules inhibitors available, future trials will help define the optimal combinations and sequence, as well as to implement these therapies with radiosurgery. A further understanding of disease pathogenesis will promote new strategies to overcome tumor resistance and develop personalized treatment plan based on the tumoral signature and the microenvironment phenotype.