Primary chemotherapy was first attempted in the early 1970s in an attempt to improve local control and survival in patients with large breast tumors. While it is now clear that primary chemotherapy can achieve high response rates and allow more conservative surgery, it is less apparent if survival is improved in these patients. It is logical, then, to consider moving this form of treatment to an earlier stage of disease in which the probability of resistant clones is less in patients with lower tumor burden. Many questions still remain unanswered in the evaluation of the role of primary chemotherapy in the treatment of early breast cancer: Is the best method of diagnosis fine needle aspiration or incisional biopsy? What diagnostic tests are important before chemotherapy? Can better conservative local treatment be achieved using the primary modality of chemotherapy? Is local control, disease response, and/or survival improved by using chemotherapy before local measures? Several important studies have been performed in the treatment of early stage disease with primary chemotherapy and will be discussed with these questions in mind. In addition, investigation of markers that predict response to chemotherapy may help us better select patients who would benefit from primary chemotherapy. Those patients who are determined to have a poorer prognosis would be candidates for novel investigational treatments.