Amplification or overexpression of HER-2/neu occurs in 30% of human breast and ovarian cancers and is associated with a poor clinical outcome, including short survival and time to relapse. Recent advances in our understanding of HER-2/neu signaling pathways have significantly increased our understanding of the tumorigenesis of breast cancer and provided new targets for treating breast and ovarian tumors that overexpress HER-2/neu. In this review, we focus on the new signaling pathways mediated by HER-2/neu in breast cancer and discuss our understanding of these pathways, as they seem to be particularly important in mediating cell survival and growth under a wide variety of circumstances in breast cancer.