In most solid tumors, it is distant metastases rather than the primary tumor which limit the prognosis. Distant metastases are caused by circulating tumor cells (CTCs) which actively invade the blood stream, attach to the endothelium in the target organ, invade the surrounding parenchyma, and form new tumors. Among many other capabilities such as migration or immune escape, CTCs require tumor-forming capacities and can therefore be considered stem cell-like cells. This chapter describes the enrichment and isolation of live CTCs from clinical blood samples for molecular characterization and other downstream applications.