In recent years, melanoma research has undergone a renaissance. What was once viewed, at least in the metastatic setting, as an intractable and untreatable disease is now revealing its molecular weaknesses. 2011 was a landmark year for melanoma therapy, with two new agents, the anti-CTLA4 antibody ipilimumab and the BRAF inhibitor vemurafenib, shown to confer a survival benefit in randomized phase III clinical trials. Overlooked in the recent flurry of interest that has accompanied the development of these drugs, melanoma is in fact an ancient disease that has long frustrated attempts at therapeutic interventions. In this article, we trace the history of melanoma: from the earliest known cases of melanoma in pre-Colombian South America, through the explorations of the Victorian anatomists right up to the molecular biology revolution of the 20th century that allowed for the identification of the key driving events required for melanomagenesis. We further outline how observations about melanoma heterogeneity, first made over 190 years ago, continue to drive our efforts to reduce melanoma to the level of a chronic, manageable disease and ultimately to cure it entirely.