Positron emission tomography (PET)-based biologic radiation planning has the potential to improve tumor control by improving the accuracy of radiation delivery, allow for rational adaptive treatment, and decrease the likelihood of both acute and late side effects. 18F-fluorodeoxyglucose (FDG) PET is a widely used and effective diagnostic tool for many metabolically active tumors, including lymphoma and lung, head and neck, gastrointestinal, and gynecologic cancers. For these tumors, PET evidence has initially focused on more accurate staging but is evolving to allow for the escalation or deescalation of the radiotherapy dose depending on the PET-determined response to initial therapy. For gliomas and prostate cancer, novel tracers offer opportunities to improve tumor targeting of areas not well identified by traditional FDG PET. These tracers may also identify functional regions of healthy organs, allowing for more effective sparing of normal tissue.