Glioblastoma multiforme is the most common and most malignant primary brain tumour. Prognosis after diagnosis remains poor despite recent advances in adjuvant therapy. Treatment of choice is gross surgical resection and combined radio-chemotherapy with temozolomide as chemotherapeutic agent. Experimental continuous low-dose chemotherapy with temozolomide in combination with a cyclooxygenase-2 inhibitor has shown encouraging effects on progression-free survival and overall survival in patients, but leads to a high proportion of distant recurrences. Here, we describe extreme far-distant metastases along the neural axis of glioblastoma multiforme in four patients receiving metronomic antiangiogenic chemotherapy and review the literature to discuss possible mechanisms.