BACKGROUND: Research efforts in neurorehabilitation technologies have been directed towards creating robotic exoskeletons to restore motor function in impaired individuals. However, despite advances in mechatronics and bioelectrical signal processing, current robotic exoskeletons have had only modest clinical impact. A major limitation is the inability to enable exoskeleton voluntary control in neurologically impaired individuals. This hinders the possibility of optimally inducing the activity-driven neuroplastic changes that are required for recovery. METHODS: We have developed a patient-specific computational model of the human musculoskeletal system controlled via neural surrogates, i.e., electromyography-derived neural activations to muscles. The electromyography-driven musculoskeletal model was synthesized into a human-machine interface (HMI) that enabled poststroke and incomplete spinal cord injury patients to voluntarily control multiple joints in a multifunctional robotic exoskeleton in real time. RESULTS: We demonstrated patients' control accuracy across a wide range of lower-extremity motor tasks. Remarkably, an increased level of exoskeleton assistance always resulted in a reduction in both amplitude and variability in muscle activations as well as in the mechanical moments required to perform a motor task. Since small discrepancies in onset time between human limb movement and that of the parallel exoskeleton would potentially increase human neuromuscular effort, these results demonstrate that the developed HMI precisely synchronizes the device actuation with residual voluntary muscle contraction capacity in neurologically impaired patients. CONCLUSIONS: Continuous voluntary control of robotic exoskeletons (i.e. event-free and task-independent) has never been demonstrated before in populations with paretic and spastic-like muscle activity, such as those investigated in this study. Our proposed methodology may open new avenues for harnessing residual neuromuscular function in neurologically impaired individuals via symbiotic wearable robots.