Melanoma (melanoma malignum) is a malignant tumor derived from melanin-producing melanocytes. Both environmental factors and genetic predisposition are important in tumor development and progression. If not detected and removed early, it is very aggressive and unresponsive to current therapeutic approaches. Therefore, one of the major goals of melanoma research is to better understand cancer biology, which in turn might result in the development of novel treatment strategies. This article reviews selected aspects of the molecular biology of melanoma with an emphasis on describing the role of transcription factors. These regulatory proteins modulate the expressions of genes, and alterations in transcription factor function are associated with human diseases, including cancer. The transcription factors MITF, NF-kappaB, AP-1, AP-2alpha, Notch, CREB, Ets-1, LEF/TCF/beta-catenin, PAX3, Ski, Snail, and STAT play important roles during the development and progression of melanoma. Both the causes and the consequences of changes in transcription factor expression and/or activity are described based on the most recent literature.