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Current treatments for late stage disease have shown higher efficacy when treated at a lower disease burden. Thus, blood\u2010based biomarkers capable of detecting melanoma prior to clinically evident distant metastasis, will improve the treatment and outcomes for melanoma patients. To that end, effective treatment of melanoma necessitates identification of patients at risk for developing distant metastases. Furthermore, employing blood biomarkers that monitor cancer progression over the course of treatment is a promising solution to post\u2010treatment drug resistance often developed in melanoma patients. Non\u2010invasive blood biomarker assays allow for regular dynamic monitoring of disease. \u201cLiquid Biopsy\u201d of blood, which exploits circulating tumor cells (CTCs), cell\u2010free circulating tumor DNA (ctDNA) and cell\u2010free circulating microRNA (cmiRNA), has been shown to detect prognostic factors for relapse in AJCC stage III and stage IV melanoma patients. Moreover, molecular characterization of CTC and analysis of various forms of ctDNA present promising potential in development of individualized therapy for melanoma patients. New approaches such as massive parallel sequencing (MPS) provide a comprehensive view of the disease progression, allowing for the selection of therapeutic options for individual patients. 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