Metastatic breast cancer develops in approximately 50% of women diagnosed with breast cancer. The optimal treatment for patients with metastatic breast cancer has yet to be defined, owing to the heterogeneity of this group and the available agents. Patients with metastatic breast cancer often receive single-agent treatment in sequence as it is unclear whether combination therapy with cytotoxic drugs offers an overall disease-free survival benefit and single agents may offer less toxicity. The advantages of combination cytotoxic therapies have included higher response rates. However, such trials have not stratified on rapidity of disease progression or on tumor bulk. In previous studies, docetaxel is one of the few cytotoxic agents to demonstrate a survival benefit in anthracycline-resistant patients and thus it has become a vital component of cytotoxic therapy. Capecitabine is also an important oral drug and has demonstrated activity in patients pretreated with anthracyclines and taxanes. Recent preclinical and clinical trials of this combination have demonstrated an increased time to tumor progression and overall survival benefit. Paclitaxel combined with gemcitabine has been compared with docetaxel plus capecitabine, with similar response rates and survival benefits. As patients on these trials have not received uniform crossover to the other active agent, whether or not the combination therapy offers an advantage for the entire cohort of metastatic patients or may be indicated for specific subgroups remains uncertain. Combination treatments may be preferable to sequential therapy for patients requiring urgent reduction in their tumor burden. Combinations of cytotoxic agents in combination with biological agents are currently being defined.