We are developing point-of-care devices using microfluidic technologies for capturing circulating tumor cells from peripheral blood of cancer patients. These cells, called circulating tumor cells (“CTCs”), provide a cellular link between the primary malignant tumor and the metastatic sites, and thus, the ability to non-invasively isolate CTCs from the blood of cancer patients has far-reaching diagnostic, prognostic, therapeutic, and basic cancer biology implications. The major challenge for such isolation stems from the fact that, CTCs are very rare in patients with cancer, comprising as few as only 1 to 10 cells/mL of blood, beyond the limits of current cell separation technologies. Recently, we have developed a novel microfluidic platform capable of selective separation of CTCs from the peripheral blood of cancer patents. Using this technology, we successfully demonstrated the capture of CTCs from patients with lung, prostate, colon or pancreatic tumors. This technological advance has important clinical implications and ultimately could be applied as a point-of-care high-throughput diagnostic device and for longitudinal follow-up of cancer patients for tailored targeted therapy.