Cancers of the central nervous system are among the most lethal of human neoplasms. They are recalcitrant to even intensive multimodality therapies that include surgery, radiotherapy, and chemotherapy. Moreover, especially in children, the consequences of these therapies can itself be devastating and involve serious cognitive and developmental disorders. It is small wonder that such cancers have come under the intense scrutiny of each of the subspecialties of clinical care and investigation as well as attracting some of the best basic research scientists. Their joint efforts are gradually peeling away the mysteries surrounding the genesis and progression of these tumors and inroads are being steadily made into understanding why they resist therapies. This makes it an especially opportune time to assemble some of the best investigators in the field to review the ‘‘state of the art’’ in the various arenas that comprise the assault on CNS tumors. The breadth of this effort by the clinical and basic neuro-oncology community is quite simply amazing. To a large extent, it evolves from the knowledge of the human genome and its regulation that has been hard won over the past two decades.