The goal of cancer vaccines and immunotherapies is to train the immune system to recognize cancer cells and destroy them. Immune responses play a dynamic role in the development of cancers, from immunosurveillance to immune escape; from in situ immune dysregulation to metastatic spread. The systematic identification and targeting of molecules involved in the immune response has led to a wide variety of potential immunotherapeutic targets for the treatment of breast cancer. Extraordinary advances in molecular immunology have led to a detailed understanding of tumor antigens, antigen presentation, innate immunity, cytokine and chemokine pathways, and immunoregulation. Many of these vaccine therapies are already in clinical development. It is the rational and rapid translation of these scientific discoveries into effective therapies for patients with breast cancer that poses the greatest challenge, and opportunity, to realize the potential of tumor vaccine therapy for breast cancer.