The updated 2016 edition of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System (CNS) uses molecular parameters and the histology to define the main tumor categories for the first time. This represents a shift from the traditional principle of using neuropathological diagnoses, which are primarily based on the microscopic features, to using molecularly-oriented diagnoses. Major restructuring was made with regard to diffuse gliomas, medulloblastomas and other embryonal tumors. New entities that are defined by both the histological and molecular features include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, wingless (WNT)-activated and medulloblastoma, sonic hedgehog (SHH)-activated; and embryonal tumor with multilayered rosettes, C19MC-altered. In addition, some entities that are no longer diagnostically relevant—such as CNS-primitive neuroectodermal tumor—have been deleted from this updated edition. The WHO2016 certainly facilitates clinical and basic research to improve the diagnosis of brain tumors and patient care.