Grade IV glioma (glioblastoma) is one of the most common brain/central nervous system cancers. In 2005, the standard of care for adjuvant treatment was significantly changed with the approval of temozolomide. Carmustine wafers have also gained some popularity. Phase III trials are currently evaluating bevacizumab in conjunction with the standard temozolomide regimen. Despite these recent advances in pharmacotherapy, roughly two-thirds of patients do not survive longer than 2 years after diagnosis. Meanwhile, the costs of treatment are substantial. The goal of this study is to review the clinical, cost-of-illness, and cost-effectiveness literature relevant to treating glioblastoma. Estimates of the economic burden of glioblastoma within different healthcare systems were converted to 2013 US dollars. Temozolomide has demonstrated a 2.5-month increase in overall survival and a 1.9-month increase in progression-free survival, relative to radiotherapy alone. Carmustine wafers have also been shown to increase overall survival by 2.3 months, compared with placebo wafers. Cost-effectiveness studies of temozolomide have produced incremental cost-effectiveness ratios, adjusted to 2013 US dollars, with a range from US$73,586 per quality-adjusted life-year (QALY) (UK National Health Service perspective) to US$105,234 per QALY (US societal perspective). More research is needed to quantify the full societal burden of illness.