The discovery of the sensitivity to chemotherapy of oligodendroglial tumors has greatly increased the interest in this tumor type. After the first studies showing the activity of chemotherapy with procarbazine, lomustine (CCNU), and vincristine (PCV), it is now clear that temozolomide is also effective in this tumor type. Fifty percent to 70% of patients with recurrent oligodendroglial tumors may respond to chemotherapy. The histological diagnosis of oligodendroglial tumors is still subject to a significant observer bias. This variation appears to be one of the causes of the recent relative increase in incidence of oligodendroglial tumors. Genetically, 60% to 70% of oligodendroglial tumors are characterized by the loss of the short arm of chromosome 1 (1p) and the loss of the long arm of chromosome 19 (19q). Virtually all tumors with the combined loss of 1p/19q respond to chemotherapy, which has been the first demonstration of the clinical usefulness of the genotyping of brain tumors. These tumors also more often have a classical oligodendroglial histology and have a much better prognosis than oligodendrogliomas without 1p/19q loss. Although the belief is widely held that in the near future the genotype of oligodendroglial tumors may help in selecting patients for treatment, this assumption has not been proven. Prospective trials on oligodendroglial tumors with analyses of the genotype are needed before such conclusions can be drawn. In the meantime it is clear that ultimately all patients with oligodendroglial tumors die of their disease, and that novel treatments are required to improve prognosis. For an improved prognosis, a better understanding of the aberrant pathways and the driving force behind these tumors is required.