Temozolomide (TMZ) is an alkylating agent earlier approved for recurrent anaplastic astrocytoma and approved for the treatment of newly diagnosed glioblastoma in the USA and Europe in 2005. TMZ shows good blood-brain barrier penetration and exhibits a favorable side effect profile. Its key mode of action appears to be methylation at N(7) and O(6)-positions of guanine. The level of expression and activity of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase is thought to be a major predictor of response to TMZ. The demonstration of prolonged survival when TMZ was added to radiotherapy in the European Organisation for Research and Treatment of Cancer 26981/22981/NCIC CE.3 trial has been a breakthrough in the treatment of newly diagnosed glioblastoma. The early preliminary evidence for activity in recurrent malignant gliomas further resulted in a broad evaluation of TMZ for other tumors in neuro-oncology, mainly low-grade gliomas, brain metastases and primary cerebral lymphomas.