The latest fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) has been built on the prior WHO 2016 classification as well as recommendations put forward by seven updates of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT). Various new tumor types and subtypes have been recognized which are of clinical significance. Tumor groups have been restructured and the nomenclature of some tumor types has also been revised. The use of terms 'entity' and 'variant' have been replaced by 'type' and 'subtype'. Significant changes have been introduced in the grading of tumors viz. use of Arabic numerals, grading within individual tumor types and combined histological and molecular grading. The terms 'Not otherwise specified' and 'Not elsewhere classified' can now be used for all tumor types. WHO CNS5 also for the first time endorses the use of DNA methylation profiling for the diagnosis of some tumor types/subtypes. Finally, the importance of combining histology with molecular parameters is emphasized for the "layered reporting" and "integrated diagnosis", which will provide valuable diagnostic, prognostic, and predictive information, as well as for some entities, suggest targeted therapies.