Oligodendrogliomas are a distinct subgroup of brain tumors with a fairly favorable clinical prognosis. However, these tumor exhibit varying degrees of heterogeneity and their clinical behavior is therefore not always the same. For this reason, genetic markers have been developed to further guide the clinical treatment. One such marker, the 1p and 19q chromosomal deletions, has been well documented in a subset of patients with oligodendrogliomas. Most importantly, patients who exhibit these chromosomal deletions respond favorably to chemotherapy. This article reviews the evidence describing the association of such deletions with a favorable response to chemotherapy and improved prognosis of patients with oligodendrogliomas. In addition, attempts to elucidate the molecular mechanisms behind the biologic behavior of these tumors are further explored.