Many clinical studies have been undertaken to assess the therapeutic potential of vaccination and have included a large variety of cancer immunogens. Most of these studies involved patients with metastatic cancer, which is characterized by the most aggressive malignant cells, the longest-lasting disease, and the failure of all standard cytotoxic treatments. The presence of tumor over long periods and the toxicity of previous treatments tend to negatively affect immune responsiveness to tumor antigens presented by the vaccine. In this review, we analyze the ability of past and current vaccine therapies to induce clinical responses in breast cancer. To date, clinical responses have been observed by using vaccines targeting HER-2/neu protein, human telomerase reverse transcriptase, carcinoembryonic antigen, and carbohydrate antigen given after stem cell rescue. The review concludes with a discussion of possible future directions for vaccine development and applications.