Majority of the cancer-related deaths are related to metastasis during which cancer cells invade the surrounding tissues, enter (intravasation) and exit (extravasation) the peripheral circulation and seed distant organs. The Circulating Tumor Cells (CTCs) exist in peripheral blood as single cells or as oligoclonal clusters of tumor cells along with platelets and lymphocytes. Detection of CTCs allows characterizing the tumors by their genotype and in predicting the prognosis and response to therapy and explants derived from these cells can be used in drug screening. In this review, we highlight the methods used for isolation and culture of CTCs and their clinical use.