Circulating tumor cells (CTCs) are rare malignant cells found in the peripheral blood that originate from the primary tumor or metastatic sites. New techniques have been developed to isolate and characterize these cells. CTC enumeration has been incorporated into different fields of oncology as a prognostic marker, a tool to monitor therapy response, and a method to understand basic tumor characteristics. This review covers the different techniques available for isolation of CTCs, the clinical utility of CTCs in breast, prostate, and colon cancer, and future directions in this field.