The oncoprotein encoded by the HER-2 oncogene is a member of the HER family of receptor tyrosine kinases and is actually the first successfully exploited target molecule in new biomolecular therapies of solid tumors. The association of HER-2 overexpression with human tumors, its extracellular accessibility, as well as its involvement in tumor aggressiveness are all factors that make this receptor an appropriate target for tumor-specific therapy. In addition, HER-2 overexpression fosters its immunogenicity, as shown by the frequency of B and T cell-mediated responses against this oncoprotein in cancer patients, and it is being investigated as a promising molecule for either passive and active immunotherapy strategies. This review summarizes a number of immune intervention approaches that target HER-2 in breast cancer. © 2005 Wiley-Liss, Inc.