The objective of this study was to review issues involved in the search for a breast cancer vaccine. A review of the recent literature (2004–2007) was undertaken, with earlier literature included as appropriate for background, to assess 1) current approaches being used to create a therapeutic breast cancer vaccine, and 2) potential strategies for a preventive vaccine targeting either an infectious agent or tumor-associated antigen. Several approaches to the development of a therapeutic vaccine show promise, including tumor cell/dendritic cell fusion and DNA vaccines based on single purified antigens or DNA fragments from whole cells. Most of these experimental vaccines have either not moved beyond preclinical testing or have not shown a significant clinical response. Strategies involving host factors that mitigate immune response against tumors also show promise. Interest has increased in developing a preventive vaccine that can be administered to immunocompetent patients with minimal or no evidence of disease. Prophylactic vaccines typically target infectious agents, but the evidence for an infectious etiology for breast cancer is largely descriptive and difficult to interpret. A second strategy for a preventive breast cancer vaccine is to target tumor-associated antigens. Ongoing clinical trials are utilizing this approach, with preliminary results that are encouraging. Cancer 2007. © 2007 American Cancer Society.