Until recently, a treatment for advanced melanoma with a tolerable side effect 
profile has remained elusive. Therefore, despite its relatively rare occurrence, 
melanoma continues to cause the majority of skin cancer deaths, with less than 
15% of those affected with late-stage disease surviving 10 years or more. 
Historically, the mainstay of treatment has been single-agent chemotherapy or 
immunotherapy with the alkylating agent dacarbazine and interleukin-2 or 
interferon. Cytotoxic chemotherapy with dacarbazine demonstrated poor response 
rates and little or no survival benefit, whereas IL-2 and interferon, although 
showing durable responses, are associated with poor side effect profiles (1, 2). 
However, with the elucidation of the molecular biology and oncogenic pathways 
involved in melanoma, agents targeted against mutations in the mitogen-activated 
protein kinase (MAPK) pathway including BRAF and MEK inhibitors have 
demonstrated prolonged survival and more manageable side effect profiles 
relative to traditional chemotherapy. Simultaneously, an evolved understanding 
of the immunologic basis for the development and regression of melanoma lead to 
the discovery of immune checkpoint inhibitors, which confer a similar survival 
benefit. Foremost among these was ipilimumab, a monoclonal antibody against the 
negative regulatory checkpoint molecule cytotoxic T-lymphocyte protein 4 
(CTLA-4), which was the first drug in the management of metastatic melanoma to 
confer a survival benefit. However, treatment is complicated by a high rate of 
grade 3 and 4 immune-related adverse events and limited response. Nivolumab, a 
fully human monoclonal antibody against programmed cell death protein 1 (PD-1), 
has shown a survival benefit in an open-label phase II trial, and was the first 
PD-1 inhibitor to be approved worldwide. With a favorable side effect profile 
and ongoing trials in combination with extant therapies, nivolumab shows 
substantial potential to further augment the options for an effective treatment 
in malignant melanoma.