Women receiving neoadjuvant systemic therapy for primary operable or inoperable breast cancer can potentially benefit in a number of ways, but the main advantage, which has been consistently demonstrated, is improved tumour resectability. Given the improvement in outcomes with the adjuvant use of trastuzumab in patients with early-stage breast cancer positive for the human epidermal growth factor receptor 2 (her2), questions have been raised about the use of trastuzumab in the neoadjuvant setting. The present paper reviews the currently available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other her2-targeted agents in the neoadjuvant setting. The panel focussed on (1) the use of trastuzumab and other her2-targeted agents as neoadjuvant therapy in primary operable, locally advanced, and inflammatory breast cancer; and (2) possible choices of chemotherapeutic regimens with trastuzumab. The suggestions described here will continue to evolve as data from current and future trials with trastuzumab and other her2-targeted agents emerge.