Study of CTC in cancer has always been hampered by its rare existence in blood. In this chapter, we discuss one of first principles employed to capture CTC from cancer patients’ peripheral blood—the affinity-based enrichment of CTC. We briefly discuss the different technologies utilizing antibodies to capture CTC based on specific antigen expression. Then we address the downstream molecular and functional characterization of CTC by utilizing these technologies. We also discuss the limitations of affinity-based CTC enrichment.