Continuous glucose monitoring, providing more detailed information on glucose excursions than single spot measurements, should help to improve the therapy in diabetic patients and is also required for feedback-controlled insulin delivery. At the Institute for Diabetes-Technology in Ulm, founded by EF Pfeiffer, a portable glucose sensor for continuous tissue glucose monitoring has been developed. The combination of microdialysis and enzymatic amperometric glucose measurement implemented in this device marked a break-through in achieving reliable and precise continuous tissue glucose monitoring. In several studies, we have demonstrated that continuous subcutaneous glucose monitoring for up to 72 hours is feasible under 'in-house' and 'daily life' conditions in diabetic patients. The measured tissue glucose concentrations correlated closely to glucose control measurements in venous and capillary blood. A reliable continuous glucose monitoring device is a prerequisite for the development of an artificial pancreas. Our group developed an algorithm for subcutaneous application of the fast acting insulin analogon lispro. In experiments performed over 7 and 24 hours good metabolic control was achieved by algorithm-based insulin application. In addition, the algorithm was able to maintain acceptable metabolic control during and after moderate physical exercise. Further work is needed to optimize continuous tissue glucose monitoring systems and to develop a closed loop system for insulin application based on continuously measured tissue glucose concentrations.