Malignant gliomas are the most common primary brain tumors in adults. In the past 10 years significant advances in the treatment of this entity have been made, mainly owing to a better understanding of molecular pathways and biological behavior of the oncogenetic process. This review treats the proven effective and promising approaches with chemotherapy. The standard care for glioblastoma is surgery and concomitant radio- and chemotherapy with temozolomide (TMZ), followed by adjuvant treatment with TMZ. It has been demonstrated to be the most effective treatment protocol. This standardized care allows the application and study of new types of treatment mainly in recurrences and nonresponding patients. Many different approaches have been investigated: the combination of cytotoxic and cytostatic agents as well as molecular targeted therapies have given some encouraging results. Further intensified regimens with TMZ and the local postsurgical application of slow-release polymers loaded with carmustine remain to be defined. The characterization of molecular markers thus becomes particularly important for the stratification of patients raising the possibility to individualize treatment.