Neoadjuvant chemotherapy for primary breast cancer is the gold standard in the treatment of locally advanced, inoperable breast cancer, but based on a large body of evidence has become a standard treatment option for patients with operable disease, who are clear candidates for adjuvant chemotherapy. Neoadjuvant chemotherapy aims at reducing mortality and improving surgical options and offers an in vivo chemosensitivity testing at the same time. It is the ideal setting for clinical and translational research. Administering chemotherapy before surgery raises some important issues concerning the choice of specific treatment regimens as well as the management of the axilla and postoperative radiotherapy. A reliable high quality diagnostic and pathological work-up is mandatory for an ideal tailoring of neoadjuvant chemotherapy. This review gives an outline of the state-of-the-art management of primary breast cancer in the setting of neoadjuvant chemotherapy.