Severe spinal cord injury (SCI) permanently abolishes motor functions caudal to the lesion. Various strategies have beenpursued to promote functional recovery after such injuries. However, none of these attempts were able to return voluntarymovements in paralyzed subjects. Here, we propose an innovative transdisciplinary research program including parallelapproaches that will converge into an integrated multi-pronged therapy able to restore voluntary movements after paralyzingSCI. To achieve this goal, we will capitalize on our recent breakthroughs that demonstrate the impressive capacity ofpharmacological and electrical spinal cord stimulations to promote full weight bearing walking in paralyzed rats whencombined with rehabilitation. In Walk Again, we will improve high level control of spinal circuits with synergistic combinationsof pharmacological agents, and with the design of multisite stimulation strategies using electrode arrays. Functional electricalstimulation of muscles will provide complementary low level tuning capacities to adjust limb motion. To allow voluntary control,we will establish a new line of research and pioneer brain-spinal interfaces by which cortical modulations will directly adjuststimulations of spinal circuits and muscles. In the final stages, we will enable neurorehabilitation with this cortico-spinalneuroprosthesis in the presence of anti-NogoA regenerative therapy. The underlying objective is to devise a fully-operativeneuroprosthetic system that will enable self-driven rehabilitation in a permissive plastic environment. Walk Again will fertilizefrontier research with pioneer ideas that will increase European competitiveness while paving the way toward viable clinicalapplications to restore function in paralyzed individuals.