Melanoma is one of the most aggressive and treatment resistant human tumors with mortality rates above 50% for metastatic skin melanoma and up to 80% for metastatic ocular melanoma. The identification of BRAF mutations in skin melanoma has led to the introduction of mutant-specific BRAF inhibitors in the clinic. While mutant BRAF inhibition invokes impressive anti-tumor response initially, unfortunately, all patients rapidly acquire resistance to these drugs. Relapse can be postponed - but not avoided - when BRAF inhibitors are combined with selective MEK1/MEK2-inhibitors. Although encouraging, these observations highlight the need for additional therapeutic strategies for cutaneous melanoma. In line with this, no effective therapies are available for patients with metastatic ocular melanoma, resulting in median survival rates of 2-8 months.