High-grade gliomas (WHO grade III anaplastic astrocytoma and grade IV glioblastoma multiforme) are the most common primary tumors in the central nervous system in adults. Unfortunately, despite great efforts in finding better therapies, high-grade glioma remains among the most devastating and deadliest of all human cancers. During recent years, genetic and molecular alterations that underlie this disease have been identified and advanced our basic knowledge about gliomagenesis. Moreover, understanding the molecular biology has also led to the development of genetically engineered mouse models that resemble many of the features of human gliomas. Ideally, such "patient-like" models should be instrumental for preclinical testing of novel therapeutics, but thus far they have not yet been widely implemented for this purpose. This review will discuss the advantages and shortcomings of the established high-grade glioma mouse models with emphasis on their potential applicability for preclinical testing of novel drugs and treatment regimens.