Trastuzumab has an established role for the treatment of HER2-positive early-stage breast cancer because of the success of this agent in the adjuvant setting. Several key questions about the value of trastuzumab for the treatment of breast cancer, however, still need to be answered. Various differences in patient characteristics and treatment regimens were present in the randomized trials discussed in this Review; therefore, the details of trastuzumab use need clarification. For example, the optimum timing, the ideal administration schedule, and the appropriate length of treatment are not known. Cardiotoxicity is major concern even though the results of all randomized trials have shown that the degree of cardiotoxicity with trastuzumab is acceptable -- the incidence of cardiac damage caused by trastuzumab ranged from 0.4% to 4.1% in the different trials (cumulative incidence of congestive heart failure, New York Heart Association class 3-4). Current data do not support the use of trastuzumab for more than 1 year. The analysis of 2-year treatment with trastuzumab is expected to be available in 2009.