Objective: This paper aims to analyse the human musculoskeletal and energetic adaptation mechanisms when physically interacting with a unilateral knee orthosis during treadmill walking. Methods: Test subjects participated in two walking trials, whereby the orthosis was controlled to deliver five predefined torque profiles of different duration (as % of a gait cycle). The adaptations to assistive torques of different duration were analysed in terms of gait parameters, metabolic effort, and muscle activity. Results: Orthotic assistances kinematic effects remain local to the assisted leg and joint, unlike the muscles spanning the knee joint, which engage in a balancing-out action to retain stability. Duration of assistive torque significantly affects only the timing of the knee joints peak flexion angle in the stance phase, while the observed joint kinematics and muscle activity demonstrate different recovery times upon changing robotic support (washout effects). Conclusion: Human body adaptations to external robotic knee joint assistance during walking take place on multiple levels and to a different extent in a joint effort to keep the gait stable. Significance: This paper provides important insights into the human bodys multiple adaptation mechanisms in the presence of external robotic assistance.