BACKGROUND Treatment of recurrent anaplastic glioma and glioblastoma remains a particular challenge in neurooncology. The lack of controlled trials results in poor evidence for all therapeutic options. Upon recurrence, many patients are treated with bevacizumab or one of the frequently used nitrosoureas such as lomustine. However, patients who still present in overall good condition after failure of multiple lines of therapy may ask for additional therapy. METHODS Here, we report our experience with the use of carboplatin in combination with etoposide as fourth- or fifth-line therapy in patients with progressive high-grade glioma. RESULTS The median Karnofsky performance status at the beginning of treatment was 80%. The median progression-free survival (PFS) was 2.5 months. PFS at 6 months was 0%. Administration of carboplatin and etoposide was associated with grade 3 or 4 hematotoxicity in 8 of 12 patients. CONCLUSION Carboplatin in combination with etoposide has an unfavorable risk-benefit profile in heavily pretreated glioma patients.