Circulating tumor cells (CTCs) provide unique information for the management of breast cancer patients, since their detection and monitoring is useful for prognosis, prediction of response to therapy, or monitoring clinical course in patients with localized or metastatic disease. Currently, the most practical application of CTCs is monitoring of patients with metastatic disease. Elevated CTC levels prior to initiation of a new systemic therapy are associated with a worse prognosis while persistently elevated CTC levels strongly suggest that the therapeutic regimen with which the patient is being treated is not working. New areas of research are directed toward developing novel sensitive assays for CTC molecular characterization. Molecular characterization of CTCs is very important for the future use of CTCs as targets of novel therapies. This review has focused on the presentation of recent data showing that CTCs are emerging as novel tumor biomarkers for prognostic and predictive purposes in breast cancer.