Though serum tumor markers and circulating tumor cells (CTCs) have been available to the oncologist for many years, their place in the management of breast cancer remains unclear. Due to issues with sensitivity and specificity, tumor markers are unreliable for the detection of metastases in early stage breast cancer. For patients with metastatic breast cancer without measurable disease (e.g., bone-only disease, pleural effusions, or ascites), it is reasonable to obtain baseline values of serum tumor markers and attempt to correlate them with the first set of scans. In patients with elevated markers at baseline whose tumor marker levels decrease in correlation with an improvement in clinical symptoms, it may be reasonable to use them in conjunction with imaging to help determine whether there is progression of disease. CTCs have been found to hold strong prognostic value for breast cancer in both the early stage and metastatic settings. No large prospective studies to date, however, have shown any predictive value for CTCs and their clinical utility is therefore limited. Whether changing treatment in response to an increase in CTCs without radiologic progression results in improvements in quality of life or survival remains to be seen. CTCs hold great promise in the management of breast cancer and future studies will help delineate their role more appropriately.