The role of high-dose chemotherapy in breast cancer is still controversial despite 20 years of clinical studies. Several nonrandomized studies had demonstrated improvement for patients with primary breast cancer. This led to the premature acceptance of high-dose therapy as a new standard of care for patients with high-risk breast cancer. There followed a phase of disillusionment after some of the randomized studies did not show any significant benefit and after a case of scientific misconduct. High-dose chemotherapy studies in breast cancer have been unpopular for the last 5 years. There is new evidence that warrants a new critical look. Fourteen randomized studies with a total of 5,592 patients have been carried out in patients with high-risk breast cancer on adjuvant therapy. Some of them showed significant improvement; others are coming to maturation now. In all randomized studies high-dose therapy in metastatic breast cancer leads to an equivalent or better disease-free survival, but because of their low power, none of these studies achieved an improvement in overall survival. It is thus necessary to perform a meta-analysis of all these studies to acquire insight into the choice of high-dose regimens. It is further necessary to look at the biology of breast cancer in the context of high-dose chemotherapy studies.