Malignant gliomas represent an heterogeneous group of brain tumors both in terms of natural history and response to treatment. The standard therapeutic approach for treating glioblastomas is a combination of radiotherapy and concomitant/adjuvant temozolomide, and methylguanine-DNA methyltransferase promoter methylation is now recognized as an important factor for predicting both prognosis and response to alkylating agents. In the future, the discovery of targeted therapies will increasingly allow personalized medical treatments. Anaplastic oligodendroglial tumors display a better prognosis and are more chemosensitive than glioblastomas; the discovery of molecular factors of prognostic significance, such as 1p/19q codeletion, will lead to different treatment strategies for different subgroups of patients. Gliomatosis cerebri is a rare diffuse glioma, and upfront chemotherapy is increasingly being employed instead of whole-brain radiotherapy to avoid/delay cognitive defects in long surviving patients, despite the lack of data to support this.