Targeted therapy is gaining prominence in the management of different cancers. Given different mechanism of action compared with traditional chemoradiotherapy, selection of patients for targeted therapy and monitoring response to these agents is difficult with conventional imaging. Various new PET radiopharmaceuticals have been evaluated for molecular imaging of these targets to achieve specific patient selection and response monitoring. These PET/computed tomography (CT) agents target the cell surface receptors, hormone receptors, receptor tyrosine kinases, or angiogenesis components. This article reviews the established and potential role of PET/CT with new radiopharmaceuticals for guiding targeted therapy.