The survival outcome of patients with malignant gliomas is still poor, despite advances in surgical techniques, radiation therapy and the development of novel chemotherapeutic agents. The heterogeneity of molecular alterations in signaling pathways involved in the pathogenesis of these tumors contributes significantly to their resistance to treatment. Several molecular targets for therapy have been discovered over the last several years. Therapeutic agents targeting these signaling pathways may provide more effective treatments and may improve survival. This review summarizes the important molecular therapeutic targets and the outcome of published clinical trials involving targeted therapeutic agents in glioma patients.