Sophisticated molecular techniques that have recently become available permit analysis of genome-wide changes in gene copy number (DNA) or expression (RNA). These genomic strategies have the potential to transform our view of cancer biology and pathogenesis. This review surveys the studies performed using genome-wide analyses of melanoma, primarily in patient specimens but also in selected experimental models of melanoma. The insights gained and the challenges and potential of these approaches are discussed with respect to their ability to dissect out the molecular events that are responsible for melanoma progression.