Tumors of the CNS frequently have devastating consequences in terms of cognitive and motor function, personality and mortality. Despite decades of work, current therapies have done little to alter the course of these deadly diseases. The discovery that chaperones/heat-shock proteins play an important role in tumor biology and immunology have sparked much interest in utilizing these proteins as targets of therapeutics, or as therapeutics themselves, in the treatments of a variety of cancers. Neuro-oncology has only recently taken notice of these entities, and the purpose of this review is to provide a background, an update and a view to the future for the roles of chaperones/heat-shock proteins in the treatment of brain tumors.