Advances in breast cancer continue to focus on the development of novel agents as well as the development of novel combinations, with the major therapeutic goal of treatment strategies revolving around improving response rates, delaying the time to disease progression, palliating symptoms, and improving quality of life. The taxanes are recognized as some of the most active single agents in breast cancer and demonstrate remarkable activity with manageable toxicity in combination with gemcitabine. Gemcitabine, a novel S-phase specific cytidine nucleoside analogue of deoxycytidine, has broad antitumor activity with significant monotherapy activity in breast cancer, with response rates ranging from 22% to 42% depending on the pretreatment characteristics of the patients. In general, gemcitabine s favorable single-agent activity and novel mechanism of action, in addition to its largely nonoverlapping toxicities, have facilitated its further development in combination with a variety of chemotherapy agents, including the taxanes. Several phase I and II trials have reported impressive activity for the gemcitabine/taxane doublet with the suggestion of clinical synergism between these 2 classes of agents. Given the remarkable and durable activity reported for this doublet, subsequent phase II trials have focused on optimizing doses and schedules. Unmistakably, these trial results are clear improvements over the single-agent activity of the taxanes in metastatic breast cancer, with the recently reported phase III trial comparing gemcitabine plus paclitaxel versus paclitaxel alone clearly reinforcing the superior outcomes demonstrated for the combination. Either as a single agent or in combination with the taxanes, gemcitabine remains a rational choice for the treatment of breast cancer.