Dramatic therapeutic benefits of targeting specific signal transduction pathways in some cancers have pushed rational molecular targeting to the forefront of cutting-edge cancer therapy. The identification and targeting of pathways critical to the phenotype of cancers offers new hope in the treatment of many patients. Transforming growth factor beta (TGF-beta) is a multifunctional cytokine that is frequently expressed in multiple types of malignant brain tumors. TGF-beta exerts a complex set of effects in cancers with an early tumor suppressive effect through growth inhibition but later effects in cancer development that are tumorigenic - including increased tumor cell motility and invasion, induction of angiogenesis, and immune suppression. Early preclinical and clinical studies have shown promise of anti-TGF-beta strategies in the treatment of malignant gliomas suggesting TGF-beta may be a potential new therapeutic target in neuro-oncology.