The combination of gemcitabine and paclitaxel in metastatic breast cancer is attractive because of the good single-agent activity of each, the different mechanisms of antitumor effect, and the, generally, nonoverlapping toxicity profiles of the agents. Phase II trials of the combination indicate response rates of 45% to 55% and median survival of 12 months in extensively pretreated patients, including those with anthracycline-resistant disease, and a response rate of 69% in patients with newly recurrent metastatic breast cancer. The combination was well tolerated, with severe hematologic toxicity being infrequent. The combination of gemcitabine, paclitaxel, and trastuzumab in patients with HER2-positive metastatic breast cancer with no prior chemotherapy in the metastatic setting produced a response rate of 71% and median response duration of 11 months. The combination was safe and well tolerated, with no unexpected toxicities being observed. Both combinations warrant additional study in metastatic breast cancer.