Glioblastoma has long proven to be a challenging disease in regard to chemotherapeutic delivery as it grows within a privileged site protected by the selective blood-brain barrier. For many years biodegradable polymers were investigated as potential drug delivery systems. However, polymer technology in the drug delivery setting only truly advanced after the polyanhydrides were tested and demonstrated to be safe and effective platforms for controlled delivery of hydrolytically unstable chemotherapeutics. An in-depth series of biochemical and preclinical studies laid the foundation for the translation of these findings into clinical use for the treatment of glioblastoma with carmustine. This chapter provides the historical perspective of the carmustine implants through preclinical safety, intracranial distribution, and efficacy studies to clinical trials in recurrent and newly diagnosed glioblastoma and subsequent FDA approval of this chemotherapeutic delivery concept. Moreover, these studies provide a successful framework on which to expand in this new era of targeted and controlled drug delivery.