After outbreaks of duodenoscope-transmitted infection with multidrug-resistant organisms, it has become clear that institutions must optimize their endoscope reprocessing programs. Standard endoscope reprocessing practices may not represent the ideal approach for preventing transmission of infection related to endoscopy. We discuss multiple approaches to enhance and optimize reprocessing, drying, and storage of standard duodenoscopes. The optimal enhanced duodenoscope reprocessing modality remains to be determined. Acknowledging the challenges and limitations in effectively reprocessing duodenoscopes, the FDA issued a safety communiqué recommending transitioning to either single use disposable duodenoscopes or duodenoscopes with innovative designs that allow more effective reprocessing.