The present article reviews the role of the second messenger enzyme protein kinase C (PKC) in the growth regulation of highgrade gliomas, and evaluates the efficacy of therapeutic strategies directed against PKC for blocking the proliferation of these malignancies in in vitro and in vivo models. The translation of such strategies to the treatment of patients with malignant gliomas may provide a novel approach for improving the otherwise grim outlook associated with these neoplasms.