With the reporting of five studies with different and complementary designs, but all demonstrating a similar and striking benefit from the targeted drug trastuzumab in HER2-overexpressing breast cancer, the year 2005 has profoundly marked the history of randomised adjuvant breast cancer trials. In view of the halving in recurrence risk, obtained at the real but small risk of cardiotoxicity, these results are generating hope in women affected with this aggressive form of the disease. But at the same time these results pose real challenges to healthcare authorities faced with the high cost of the anti-HER2 monoclonal antibody. These results also leave oncologists and patients to deal with a complex treatment tailoring process that needs to take into account risk of an early relapse as well as the benefit versus risk of trastuzumab according to the different patterns of administration used in the clinical trials.