The fact that local therapy of the primary tumor is futile in the presence of metastatic disease is almost considered axiomatic among oncologists. However, this perception is now being challenged by new laboratory and clinical data. Results from animal models have demonstrated that some primary tumors release factors that enter the circulation which, by mobilizing cells from bone marrow, render distant organs more receptive to metastasis. Clinical observations in renal, breast, and prostate cancer are all consistent with the hypothesis that treatment directed against the primary tumor might retard progression of existing metastases. This hypothesis is amenable to testing by randomized trials of local therapy to the primary site in patients with metastatic cancer.