The optimal management of elderly patients with glioblastoma multiforme (GBM) remains controversial, as no evidence-based standard of care exists for this unique subpopulation. These patients typically have a poor prognosis and high rates of treatment-related toxicities. Unfortunately, many elderly GBM patients are often excluded from clinical trials. Consequently, the role of chemoradiotherapy with temozolomide for elderly patients is unclear, and these patients are often treated with radiotherapy (RT) alone or palliative approaches following surgical diagnosis. However, there is emerging evidence that healthy and fit elderly patients may benefit from combined modality therapy, and aggressive therapy should be considered. Elderly patients with poor performance scores have historically been offered RT alone when treated, but preliminary data support the use of temozolomide as initial therapy. Moreover, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation appears to be a predictive marker of benefit from temozolomide. In the future, this molecular prognostic factor may be used clinically to guide therapeutic decision-making for some elderly GBM patients. Nevertheless, other factors that affect quality of life, such as number of trips to the hospital, number of ancillary tests, morbidity of treatment, and treatment costs to the patient and community should also be considered.