Viruses have been considered for use as therapeutic agents against cancer, and malignant glioma in particular. Oncolytic viruses were designed to target malignant cells supporting efficient virus replication, or rendered vulnerable to viral destruction due to tumor-specific defects in their defense against virus infection. Other than conventional cancer chemotherapy, viral antineoplastic agents require complex interactions with the host organism to reach their target and to unleash their oncolytic activity. Recent progress in the design and therapeutic application of oncolytic viruses carries the promise to make these agents available for treatment of malignant glioma.