Her-2/neu (HER2) is a protooncogene that is known to be amplified in a proportion of many different types of carcinomas. Overexpression of HER2 is generally associated with poor prognosis and resistance to chemo and radiotherapy. There exist many approaches that may be potentially utilized for therapy of HER2 overexpressing tumors. Understanding the biochemical and physiological function of HER2 in oncogenesis as well as its role in facilitating immune escape of tumor cells is critical for the improvement of existing strategies as well as developing new therapeutic candidates targeting HER2.