Melanoma, a cancer of pigment-producing cells, accounts for nearly 200,000 new cases of cancer reported each year worldwide. It is the deadliest skin cancer. Alarmingly, in the U.S., the incidence has tripled over the last three decades, and the death rate has increased at a time when mortality for other common cancers has declined. If caught early, melanoma can be successfully treated by surgery, while those diagnosed with widespread metastatic disease (Stage IV) have a median survival of less than one year. Eight new treatments have been approved since 2011 that have revolutionized the field, provided new hope for patients, and showcased melanoma as a case study for all of oncology. These therapies fall into two classes: 1) targeted therapies that block growth-promoting pathways in melanomas with activating mutations in BRAF (vemurafenib, dabrafenib, and trametinib); and 2) immunotherapies that target the “brakes” on the immune system including the checkpoint inhibitor antibodies to CTLA-4 (ipilimumab) and PD-1 (pembrolizumab and nivolumab). Despite the benefits that these FDA- and European Commission-approved treatments offer, there is a significant need for new therapeutic approaches to overcome primary and treatment-emergent resistance and lead to ever improved outcomes for patients. Through research and the engagement of all stakeholders, including academia, the pharmaceutical industry, government, patients, entrepreneurs and donors, the melanoma research community will continue to produce cutting-edge therapies whose benefits will extend beyond melanoma and impact other cancers as well.