The cyclooxygenase enzyme is a prostaglandin synthase that has two isoforms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Upregulation of the COX-2 isoform in many cancers has led to investigation regarding the potential role of this enzyme in oncogenesis. The Food and Drug Administration has approved celecoxib (Celebrex) for patients with familial adenomatous polyposis (FAP) based on a study that showed a reduction in the number of polyps in such patients when treated with high doses of this drug. We are investigating the potential role of COX-2 inhibitors in the treatment of recurrent malignant gliomas in combination with retinoids. In this article the rationale for using this combination therapy in patients with malignant gliomas is presented.