Malignant glioma is a primary tumor of the central nervous system, representing a major cause of mortality in a young, productive subset of population. The management of this neoplasm requires aggressive treatments, including radiotherapy. Accurate imaging plays a central role in treatment planning process with curative intent based on radiation therapy. In order to maximize the radiation dose to the tumor and to minimize the damage to the normal surrounding tissue, a reliable identification of viable tumor margins is indeed required. The use of PET in the treatment planning process has become more promising over the years, although many important questions must be addressed. The aim of this article is to critically review the evidence supporting PET in radiotherapy planning, with special emphasis on the role of novel radiopharmaceuticals, comparing its sensitivity and specificity with respect to 18F-FDG and other anatomic imaging modalities.