Tumors have usually been classified by their morphologic appearances. Unfortunately, these current classification schemes have serious drawbacks. They are not able to stratify similar histopathological appearances that will follow significantly different clinical courses or respond differently to chemotherapy. The information that a specific molecular profile correlates with important clinical endpoints should permit physicians to take treatment decisions based on the molecular characteristics of each tumor. Lessons from the metastatic setting have been translated to the adjuvant setting, and several strategies have been evaluated in clinical trials. The expression of estrogen receptors (ER) in breast cancer enables physicians to make treatment decisions related to the use of hormonal manipulations. In this context, the challenge is to define a suitable subgroup of patients who will benefit from the addition of chemotherapy. Otherwise, the lack of ER expression predicts no benefit from hormonotherapy. In this setting chemotherapy plays a central role. The selection of the most appropriate regimen based on HER-2 status remains an uncertain strategy. However, the expression of the oncoprotein HER-2 has been linked to the probability of response to the target-designed monoclonal antibody trastuzumab. The role of trastuzumab in the adjuvant setting is supported by the early results of three large clinical trials presented at the American Society Clinical Oncology meeting in 2005. These trials have shown a striking impact of trastuzumab on the main endpoints such as disease-free survival and overall survival. In this context, the integration of trastuzumab with taxane and anthracycline-based-chemotherapy seems to be the appropriate choice. This review will combine data from breast cancer biology with clinical evidence coming from large phase III trials in the attempt to propose a molecular targeted approach to the adjuvant treatment strategy of early breast cancer patients.