Despite the availability of a number of active cytotoxic agents and combination regimens derived from them, the median survival of patients with metastatic breast cancer (MBC) has not been dramatically prolonged and it remains largely an incurable disease. As such, common goals of treatment in this setting are to ameliorate cancer-related symptoms and maintain or improve patient quality of life for as long as possible. Achieving optimal palliation, however, requires balancing the toxicities of therapy with the cancer-controlling benefits, and, to this end, the development of effective and well-tolerated regimens is a priority. Gemcitabine, a novel nucleoside analogue with demonstrated antitumor activity and a favorable safety profile, has been evaluated in a number of recent clinical trials as single-agent therapy for MBC, including studies of first- and second-line therapy, as well as the salvage setting for patients with taxane- and anthracycline-refractory advanced disease.