This study gives an overview of glucose sensing strategies for potential use in diabetes therapy. The basis for the most commonly used amperometric glucosensors is the Clark electrode which measures oxygen tension. Coupling this sensor with glucose oxidase led to the first specific “biosensor” for glucose measurement. This sensor has been used for more than 20 years in thein vitroartificial pancreas (“Biostator”). The development of implantable glucose sensors has been hampered by the disappointingin vivobehavior of these sensors. Alternative glucose sensing techniques including noninvasive approaches are still experimental. Combining the microdialysis technique for continuous sampling of subcutaneous extra-cellular fluid with anin vitroon-line amperometric glucose oxidase electrode (the “Ulmer Zuckeruhr” or “sugar watch” system), permits continuous glucose sensing for 72 hours. Although there are differences and delays between changes in tissue and blood glucose concentrations, a complete automated feedback-controlled insulin delivery system is possible if fast acting insulin analogs can close the insulin delivery “feedback loop.”