Despite almost 30 years of clinical cancer research, the true impact of second and subsequent lines of chemotherapy on the outcome of metastatic breast cancer patients, especially on the duration of survival, is still unknown. In the virtually incurable metastatic setting, issues like quality of life and patients' preferences gain particular relevance. At the turn of the century, in-depth rethinking of the design of clinical trials run in this challenging disease setting appears to be warranted.