The incidence and mortality of melanoma has seemed to level off for certain groups after a steady increase during the last 50 years. This trend is suspected to be secondary to education efforts aimed at prevention and better detection and removal of thin, biologically benign melanomas. Since no effective systemic therapies exist for metastatic melanoma, early detection and removal of thin melanomas offer the best chance of cure. For thicker melanomas, sentinel lymph node biopsy has improved the accuracy of staging and prognostic evaluation. However, approximately one third of patients diagnosed with metastatic melanomas present without previous regional lymph node metastases. As the genomic understanding of melanoma's pathogenesis grows, new methods likely will be developed to more accurately identify the people at risk for melanoma, those who have high-risk melanomas, and those who have disseminated disease. We review current and potential biomarkers useful for the screening for and prevention, diagnosis, staging, and prognosis of melanoma.