The number of patients over 65 with newly diagnosed glioblastoma is anticipated to increase significantly in coming decades as a result of demographic shifts in the United States. Older patients with this disease have a significantly worse life expectancy compared with patients under 65. Mounting clinical evidence suggests that fit elderly patients with glioblastoma benefit from the addition of temozolomide to standard surgery and radiation. As a result, for healthy patients over 65 we recommend maximal surgical debulking followed by involved-field radiotherapy (60 Gy in 30 fractions) with concurrent temozolomide (75 mg/m(2)/day) and 6 months of adjuvant temozolomide (150-200 mg/m(2)/day for five consecutive days/month). Patients over 65 with newly diagnosed or recurrent glioblastoma should also be considered for inclusion in clinical trials. MGMT is a validated prognostic marker in patients over 65 and may be useful in clinical decision-making in frail elderly patients. Age alone should not be a factor in deciding how patients with newly diagnosed glioblastoma should be treated.