With the advent of technology that can reliably detect them, interest in circulating tumor cells have escalated with over 18,000 publications and its involvement in 911 trials. Its presence in the blood stream connotes more aggressive and serious disease. This has led to a revision in the American Joint Commission on Cancer TNM classification for breast cancer. Presence of circulating tumor cells upcodes presumed non-metastatic breast cancer (M0) to an intermediate stage M0(i+). This review will describe the methods to capture and detect circulating tumor cells with a focus on the most analytically valid system -CellSearch. The studies underpinning the established uses of CTC enumeration in prognosis of metastatic cancers (breast, prostate and colon) will be highlighted as well as the imminent deployment in early breast cancer. Emerging applications in monitoring cancer treatment and promising indications in other cancers will also be examined.