Glioblastoma (GBM) is the most malignant among astrocytic tumours and is associated with a poor prognosis. Age, performance status, mini-mental status examination score, methylation status of methylguanine methyltransferase promoter and extent of surgery constitute the main prognostic factors. Surgery aimed to complete resection should be the first therapeutic modality in the management of glioblastoma. However, complete resection is virtually impossible due to infiltrative nature of this disease and relapse is almost inevitable. Postoperative concomitant chemo-radiation is the standard treatment and consists of 60Gy of external-beam radiotherapy (to be delivered to a target volume including a 2-3cm ring of tissue surrounding the perimeter of the contrast enhancing lesion on pre-operative CT/MRI scans) plus temozolomide (TMZ) administered concomitantly (75mg/m(2) daily) and after radiotherapy (150-200mg/m(2), for 5 days every 4 weeks). At time of recurrence/progression, a nitrosourea-based chemotherapy constitutes a reasonable option, as well as a temozolomide re-challenge for patients without progression during prior temozolomide treatment.