Standard care for newly diagnosed glioblastoma multiforme (GBM) previously consisted of resection to the greatest extent feasible, followed by radiotherapy. The role of chemotherapy was controversial and its efficacy was marginal at best. Five years ago temozolomide (TMZ) was approved specifically for the treatment of recurrent malignant glioma. The role of TMZ chemotherapy administered alone or as an adjuvant therapy for newly diagnosed GBM has been evaluated in a large randomized trial whose results suggested a significant prolongation of survival following treatment. Findings of correlative molecular studies have indicated that methylguanine methyltransferase promoter methylation may be used as a predictive factor in selecting patients most likely to benefit from such treatment. In this short review the authors summarize the current role of TMZ chemotherapy in the management of GBM, with an emphasis on approved indications and practical aspects.