There is a growing body of evidence that carmustine wafer implantation during surgery is an effective therapeutic adjunct to the standard combined radio-chemotherapy regimen using temozolomide in newly diagnosed and recurrent high-grade glioma patient management with a statistically significant survival benefit demonstrated across several randomized clinical trials, as well as prospective and retrospective studies (grade A recommendation). Compelling clinical data also support the safety of carmustine wafer implantation (grade A recommendation) in these patients and suggest that observed adverse events can be avoided in experienced neurosurgeon hands. Furthermore, carmustine wafer implantation does not seem to impact negatively on the quality of life and the completion of adjuvant oncological treatments (grade C recommendation). Moreover, emerging findings support the potential of high-grade gliomas molecular status, especially the O(6)-Methylguanine-DNA Methyltransferase promoter methylation status, in predicting the efficacy of such a surgical strategy, especially at recurrence (grade B recommendation). Finally, carmustine wafer implantation appears to be cost-effective in high-grade glioma patients when performed by an experienced team and when total or subtotal resection can be archieved. Altogether, these data underline the current need for a new randomized clinical trial to assess the impact of a maximal safe resection with carmustine wafer implantation followed by the standard combined chemoradiation protocol stratified by molecular status in high-grade glioma patients.