Disabilities that follow cerebrovascular accidents and spinal cord injuries severely impair motor functions and thereby prevent the affected individuals from full and autonomous participation in activities of daily living. Rehabilitation therapy is needed in order to recover from those severe physical traumas. Where rehabilitation is not enough to restore completely human functions then functional compensation is required. In the last years the field of rehabilitation has been inspired by new available technologies. An example is given by rehabilitation robotics where machines are used to assist the patient in the execution of specific and physical task of the therapy. In both rehabilitation and functional compensation scenarios, the usability and cognitive aspects of human-machine interaction have yet to be solved efficiently by robotic-assisted solutions. Hybrid systems combining exoskeletal robots (ERs) with motor neuroprosthesis (MNPs) emerge as promising techniques that blends together technologies that could overcome the limitations of each individual one. Another promising technology which is rapidly becoming a popular application for physical rehabilitation and motor control research is Virtual Reality (VR). In this chapter, we present our research focuses on the development of a new rehabilitation therapy based on an integrated ER-MNP hybrid systems combined with virtual reality and brain neuro-machine interface (BNMI). This solution, based on improved cognitive and physical human-machine interaction, aims to overcome the major limitations regarding the current available robotic-based therapies.