Nervous system tumors are clinically challenging neoplasms that form within the central and peripheral nervous system. Although there have been many clinical trials using novel agents for the treatment of primary brain tumors, there have been few advances that positively affect overall patient survival. Over the past several years, there has been significant progress in the development of accurate small-animal spontaneous brain tumor models, small-animal neuroimaging, and tools for the bioinformatic analysis of complex molecular data sets, all of which have contributed to an improved understanding of the pathogenesis of human brain tumors. Whereas these models will continue to be of great value in basic science investigations, they can also be used to identify and validate potential therapies for brain tumors and to evaluate these drugs in preclinical trials. The National Cancer Institute recently convened a workshop to review the current state of small-animal brain tumor modeling and to make recommendations about the use of these models to improve the clinical outcome for patients with brain tumors. In this meeting report, we outline the current state of small-animal models for brain tumors, the potential applications of these models, and the recommendations made by the workshop participants for the use of mouse models in the preclinical evaluation of potential brain tumor therapies.