Circulating tumor cells (CTCs) are epithelial cells that can be found circulating in the blood of metastatic breast cancer patients and may represent a heterogeneous population including cancer stem cells and cells shed from the metastatic lesions. Interest and research continues in CTCs with the intent to detect and perform molecular analysis of those cells with the possibility to better understand the fundamental processes driving tumor metastasis. The technological advancement suggested the potential to measure the metastatic potential of a tumor at the single cell level rather than waiting until the cells established a metastatic lesion and proliferate until they are large enough to be visualized on imaging or cause symptoms. Therefore, earlier detection of these cells may be associated with more effective treatment of micrometastatic disease and lead to better outcomes. This chapter will provide an overview of the clinical utility of CTCs in breast cancer by reviewing the various techniques of CTC isolation; discussing their use as a prognostic indicator, as well as monitoring tool for response to therapy and detection of recurrence in the metastatic setting; reviewing their use in the neoadjuvant setting for prognosis and prediction of disease recurrence after surgery; evaluating CTC variation according to molecular subtype; discussing the detection of HER2+ CTCs in patients with HER2− tumors; and finally outlining ongoing trials and future directions of CTCs.