For nearly a century, glial neoplasms have been classified by microscopic features alone with treatment prescribed based on histology using a "one-size-fits-all" formula. However, recent advances in our understanding of the molecular events underlying gliomagenesis are beginning to change the way we think about the diagnostic classification of gliomas. Indeed, several recurring molecular derangements are now being viewed as cornerstones of a new diagnostic framework because these alterations appear to be superior to traditional microscopic classification schemes as guideposts for treatment selection and prognosis. Moreover, molecular analysis of tumor tissue is identifying aberrant growth signaling pathways in glioma which can now be blocked selectively by a new generation of targeted therapies, including small molecule inhibitors and monoclonal antibodies. Time will tell whether these new agents can be successfully introduced into the clinical arena. In the meantime, the molecular characteristics of gliomas are being used to select patients for both randomized trials and phase II studies.