The burden of Musculo-Skeletal (M-S) diseases and prosthetic revision operations is huge and increasing rapidly with the aging population. For patients that require a major surgical intervention, procedures are unsafe, uncertain in outcome and have a high complication rate. The goal of TLEMsafe is to create an ICT-based patient-specific surgical navigation system that helps the surgeon safely reaching the optimal functional result for the patient and is a user friendly training facility for the surgeons. TLEMsafe is developed by generating automated 3-D image-analyzing tools to parameterize the M-S system. The patient-specific parameters are fed into a recently developed M-S model with which the patient-specific functional outcome can be predicted. This consists of a direct effect (e.g. due to the removal of a muscle in a tumor patient), but has also a secondary effect in the sense that the patient will generate adaptive behavior to the altered M-S system. Implementation of the adaptive capacity will be a unique (but essential) feature which allows valid predictions of the functional effects of surgical interventions. The next step is that the surgeon can virtually operate on the patient-specific model after which the model predicts the functional effects. Once the optimal plan is selected, this is fed into a system that allows the surgeon to reproduce the selected surgical plan during the actual surgery TLEMsafe is a navigation system based on innovative ICT tools for training and pre-operative planning. Extensive, innovative validation techniques including quantitative indicators to improve safety (of surgical operation) and quality (highly predictable effects of complex surgery) are included. The emphasis on the M-S pathologies and the adaptive capabilities of the human M-S system creates a unique system. Co-developing the software of the visual and interactive (surgical) parts with clinicians and companies eases the successful introduction to (future) surgeons.