Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a tumor and metastasis suppressor gene, is critical for the regulation of the invasive and metastatic activities of tumor cells. RECK is down-regulated in some malignancies and its expression is positively correlated with survival of patients with cancer. Patients with malignant glioma have poor prognosis. Since RECK expression decreases as the tumor stage progresses from less invasive grade II glioma to invasive glioblastoma multiforme, up-regulation of RECK by natural or synthetic agents might be a valuable therapeutic option for glioma. Histone deacetylase inhibitors and non-steroidal anti-inflammatory drugs have been widely used clinically and demonstrated to increase RECK expression in cancer cells, thus they might be used as RECK inducers. In this article, the functions of RECK and the role of RECK in glioma are reviewed, with emphasis on the potential application of RECK inducers in the treatment of glioma.