The landmark Diabetes Control and Complications Trial (DCCT) showed that glucose control is critical to reducing the risk of diabetes-related complications. This chapter outlines a series of innovations and investigations that followed the DCCT, aimed at minimizing the risk of hypoglycemia while further improving glucose control. The chapter presents an example of innovations in wired enzyme technology that facilitated the movement from capillary glucose monitoring to continuous glucose monitoring (CGM) and ultimately, the first-factory calibrated CGM system. The next glycemic management innovation was to connect CGM data to an insulin pump containing an algorithm able to adjust insulin delivery based on the changing glucose levels and trends. The key features of automated insulin delivery (AID) systems, currently approved in the United States, are presented. The AID summary table includes type of pump, type and function of the insulin delivery algorithm, the data management system, and the indications for use. The next section explores the innovation of alternative routes of insulin delivery to move toward the goal of a fully automated insulin delivery system. The main trials in developing and implementing an implantable intraperitoneal programmable system are summarized. The last section explores if sensor input in addition to glucose levels such as continuous sensing of ketone, lactate, or insulin levels may provide valuable feedback to move us closer to a fully autonomous AID system. Much of this diabetes innovation and investigation work has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases over that last 75 years.