Because of the limits of wearable needle-type or microdialysis-based enzymatic sensors in clinical use, fully implantable glucose monitoring systems (IGMS) represent a promising alternative. Long-term use reducing impact of invasiveness due to implantation, less frequent calibration needs because of a more stable tissue environment around the sensor and potential easier inclusion in a closed-loop insulin delivery system are the expected benefits of IGMS. First experiences with subcutaneous and intravenous IGMS have been recently collected in pilot studies. While no severe adverse events have been reported, biointerface issues have been responsible for the failures of IGMS. Tissue reactions around implanted subcutaneous devices and damages of intravenous sensors due to shearing forces of blood flow impaired IGMS function and longevity. In functioning systems, accuracy of glucose measurement reached satisfactory levels for average durations of about 120 days with subcutaneous IGMS and 259 days with intravenous sensors. Moreover, sensor information could help to improve time spent in normal glucose range when provided to patients wearing subcutaneous IGMS and allowed safe and effective closed-loop glucose control when intravenous sensors were connected to implanted pumps using intra-peritoneal insulin delivery. These data could open a favourable perspective for IGMS after improvement of biointerface conditions and if compatible with an affordable cost.