Targeted therapies, which attack specific cancer cells without harming normal cells, have the potential to treat cancers with fewer side effects than conventional therapies. Critical to the development of this approach, is to determine which treatment is most likely to be benefit an individual patient. Currently, prostate-specific antigen (PSA) is the best routinely available biomarker providing diagnostic and prognostic information about prostate cancer. PSA testing is useful, but does not reliably determine whether or not a treatment is working, nor does not provide definitive guidance in selecting one therapy over another. My colleagues and I are evaluating promising new technologies to capture and characterize circulating tumor cells from a routine blood draw. We are finding that the number of circulating tumor cells in a patient’s blood helps determine a patient’s prognosis and whether or not a treatment is working. Circulating tumor cells are also providing a biological snapshot of an individual patient’s tumor, which may help determine the choice of therapy.