Melanoma is a cancer of the pigment-producing cells of the body and its incidence is rising. Targeted inhibitors that act against kinases in the MAPK pathway are approved forBRAF-mutant metastatic cutaneous melanoma and increase patients’ survival. Response to these therapies is limited by drug resistance and is less durable than with immune checkpoint inhibition. Conversely, rare melanoma subtypes have few therapeutic options for advanced disease and MAPK pathway targeting agents show minimal anti-tumor effects. Nevertheless, there is a future for targeted kinase inhibitors in melanoma: in new applications such as adjuvant or neoadjuvant therapy and in novel combinations with immunotherapies or other targeted therapies. Pre-clinical studies continue to identify tumor dependencies and their corresponding actionable drug targets, paving the way for rational targeted kinase inhibitor combinations as a personalized medicine approach for melanoma.