The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material studied for prognosis is either, cutaneous primaries or metastatic deposits, rather than the melanoma cells in the circulatory system which are responsible for disease progression. In this review article we discuss the potential use of circulating tumour cell (CTC) detection and quantification for identifying patients at risk of metastatic deposits. We also discuss current therapies for the treatment of metastatic melanoma and analyse how CTCs may be used to evaluate the effectiveness of current therapies and to pinpoint patients who require further treatment.