The management of de novo stage IV breast cancer focuses on systemic therapy for distant sites. The underlying assumption is that such therapy will control the primary tumor sufficiently well for the remainder of the patient's life, and that specific therapy for the primary tumor is not beneficial. This concept is being re-evaluated because of the lengthening survival of stage IV patients, the tendency towards decreasing metastatic disease burden at diagnosis, and accumulating data suggesting that local therapy for the primary site may be beneficial. Retrospective data on more than 30,000 women from North America and Europe have now been published, showing a robust association between surgery or radiotherapy for the primary tumor and prolonged survival. Many questions remain, most importantly, whether this observed association reflects a selection of women with good prognosis for primary site therapy; others relate to the fraction of women in published studies who were diagnosed with metastatic disease postoperatively, whether specific subsets would derive greater benefit, and the appropriate timing and extent of local therapy. These issues can be definitively addressed only in a randomized trial. Two trials are open in India and Turkey; a third is being planned in the United States and is expected to open in 2011. Given the importance of these questions for the approximately 10,000 women who are diagnosed with stage IV breast cancer in the United States-and the many more worldwide-it is hoped that the US trial will receive strong support from breast cancer physicians and from our patients.