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Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a ‘neural cursor’ with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis. The cover shows Matt Nagle, first participant in the BrainGate pilot clinical trial. He is unable to move his arms or legs following cervical spinal cord injury. Researchers at the Department of Neuroscience at Brown University, working with biotech company Cyberkinetics and 3 other institutions, demonstrate that movement-related signals can be relayed from the brain via an implanted BrainGate chip, allowing the patient to drive a computer screen cursor and activate simple robotic devices. Such neuromotor prostheses could pave the way towards systems to replace or restore lost motor function in paralysed humans. Prior to this advance, this type of work has been performed chiefly in monkeys. The latest example of such research has achieved a large increase in speed over current devices, enhancing the prospects for clinically viable brain-machine interfaces.