Preoperative systemic therapy with cytotoxic or biologic anticancer regimens has gained significant popularity in the management of breast cancer. Moreover, there is a worldwide paradigm shift toward an individualized approach to identify predictive surrogate markers for stratifying patients into distinct subgroups to improve outcome after neoadjuvant or adjuvant therapy. Although achievement of pathologic complete response constitutes the gold standard for assessing therapeutic efficacy only a minority of patients achieve a pathologic complete response. Imaging has evolved to play a crucial role in monitoring treatment effectiveness, particularly, early during therapy. There is mounting evidence that (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a more superior metabolic imaging modality than anatomic modalities for assessment of the response during or at completion of treatment. Ultimately, the prediction of therapeutic effectiveness or survival or both by FDG-PET imaging could successfully tailor treatment and avoid unnecessary toxicities. This paper provides an overview of current use and the main indications of FDG-PET and integrated PET/computed tomography in response assessment of breast cancer as well as the future directions for the management using non–FDG-based tracers developed against specific targets.