Neoadjuvant therapy is therapy administered before surgical intervention and while the tumor remains in the breast. It may be given to treat large, locally advanced tumors, with the aim of shrinking them and thus making their surgical excision either simply possible or less radical. Most neoadjuvant therapy is chemotherapy, but adjuvant endocrine therapy is increasingly used in hormone-sensitive tumors; for example, those responsive to tamoxifen. Repeat biopsies aimed at assessing response to treatment—for example, by examining estrogen receptor status or markers of proliferation in tumor tissue—may be taken during the course of adjuvant therapy. In this chapter, the essential protocols associated with designing neoadjuvant trials are described, methods of assessing response to neoadjuvant therapy are detailed, and various approaches to collecting appropriate clinical samples and their assessment are presented.