This chapter discusses the value of FDG-PET and combined FDG-PET/CT in staging and follow-up of melanoma patients. For melanoma patients, the presence or absence of regional lymph node metastases is one of the most important prognostic factors; the recent development of sentinel lymph node biopsy offers a highly sensitive staging method. FDG-PET has shown a limited sensitivity to detect microscopic lymph node metastases in this selected group of patients with stages I and II melanoma. However, for the detection of distant metastases, FDG-PET is frequently used. Although there is no consensus, some surgeons pursue surgical excision of metastatic disease if only one or a few sites of disease are apparent. Precise identification of the location and number of metastatic lesions could therefore be important for surgical planning. Even though patients with metastatic melanoma generally have a poor prognosis (5-year survival 3-16%), there is still a need for accurate staging. Firstly, to identify those patients who may benefit from a surgical procedure, while avoiding these potentially harmful surgical procedures for patients with multiple distant metastases. Secondly, accurate staging is important to improve the efficiency of clinical trials, and thirdly, to provide patients with detailed information about their prognosis. Taking the published literature together, and reasoning that FDG-PET/CT is the current standard in PET imaging, there may be a case for the combined PET/CT in the setting of metastatic melanoma. However, further research is needed as the benefit of the combined FDG-PET/CT vs. FDG-PET alone seems to be less than reported for other tumor entities, which may be due to the high avidity of melanoma for FDG, so that many of the metastases are detected with FDG-PET and the additional CT does not increase the sensitivity.