Background Circulating tumor cells (CTCs) are an important diagnostic tool for understanding the metastatic process and the development of cancer. Methods This review covers the background, relevance, and potential limitations of CTCs as a measurement of cancer progression and how information derived from CTCs may affect treatment efficacy. It also highlights the difficulties of characterizing these rare cells due to the limited cell surface molecules unique to CTCs and each particular type of cancer. Results The analysis of cancer in real time, through the measure of the number of CTCs in a “liquid” biopsy specimen, gives us the ability to monitor the therapeutic efficacy of treatments and possibly the metastatic potential of a tumor. Conclusions Through novel and innovative techniques yielding encouraging results, including microfluidic techniques, isolating and molecularly analyzing CTCs are becoming a reality. CTCs hold promise for understanding how tumors work and potentially aiding in their demise.