Biologically conformal radiation therapy (BCRT), a convergence of intensity-modulated radiation therapy (IMRT) and positron emission tomography (PET)-based functional imaging, incorporates patient-specific, image-derived biological information. This approach may potentially lead to a paradigm shift in radiation therapyspatially varying dose prescriptions, or dose sculpting, for individualized and dosimetrically optimized treatment. This article reviews the current status of the technical, biological, and clinical aspects of PET-guided radiation therapy. It remains unclear, however, whether PET is currently capable of delineating the true extent of viable tumor with sufficient accuracy and precision to reliably guide therapy on a routine basis.