After 40 years of research and development, today continuous glucose monitoring (CGM) is demonstrating the benefit it provides for millions with diabetes. To provide in vivo accuracy, new permselective membranes and mediated systems have been developed to prevent enzyme saturation and to minimize interference signals. Early in vivo implanted sensor research clearly showed that the foreign body response was a more difficult issue to overcome. Understanding the biological interface and circumventing the inflammatory response continue to drive development of a CGM sensor with accuracy and reliability performance suitable in a closed-loop artificial pancreas. Along with biocompatible polymer development, other complimentary algorithm and data analysis techniques have improved the performance of commercial systems significantly. For example, the mean average relative difference of Dexcom’s CGM system improved from 26 to 14 % and its use-life was extended from 3 to 7 d. Significant gains in usability, including size, flexibility, insertion, calibration, and data interface, have been incorporated into new generations of commercial CGM systems. Besides Medtronic, Dexcom, and Abbott, other major players are also investing in CGM. Becton Dickinson is conducting clinical trials with an optical galactose glucose binding system. Development of fully implanted sensor systems fulfills the desire for a discreet, reliable CGM system. Research continues to find innovative ways to help make living with diabetes easier and more normal, and new segments are being pursued (intensive care unit, surgery, behavior modification) in which CGM is being utilized.