Molecular analysis approaches hold promise to refine the management of patients with malignant gliomas. An important step in the application of these techniques to guide clinical decision-making involves transitioning these approaches from the research setting into the clinical diagnostic arena, using methods that can be performed rapidly and reliably on surgically obtained tumor specimens. Many centers have begun this process for the detection of chromosome 1p and 19q deletions in oligodendroglial neoplasms. It is likely that the current limited portfolio of prognostic markers will be increased substantially during the next several years as innovative techniques for tumor genotyping and gene expression profiling help to identify additional correlates of tumor prognosis. An associated challenge involves demonstrating that biological stratification can support therapeutic stratification that will influence, rather than merely predict, the outcome of patients with brain tumors. The realization of this long-range goal will require the identification of novel therapeutic strategies that hold promise for improving the outcome of molecularly defined subsets of high-grade gliomas, which as a group remain largely resistant to conventional therapies.