The comprehensive molecular profiling of cancer has dramatically altered conceptions of numerous tumor types, particularly with regard to their fundamental classification. In the case of primary brain tumors, the widespread use of disease-defining biomarker sets is profoundly reshaping existing diagnostic entities that had been designated solely by histopathological criteria for decades. This review describes recent progress for diffusely infiltrating gliomas of adulthood, the most common primary brain tumor variants. More specifically, it details how routine incorporation of a handful of highly prevalent molecular alterations robustly designates refined subclasses of glioma that transcend conventional histopathological designations.