Advances in our understanding of the physiological basis of locomotion enable us to optimize the neurorehabilitation of patients with lesions to the central nervous system, such as stroke or spinal cord injury (SCI). It is generally accepted, based on work in animal models, that spinal neuronal machinery can produce a stepping-like output. In both incomplete and complete SCI subjects spinal locomotor circuitries can be activated by functional training which provides appropriate afferent feedback. In motor complete SCI subjects, however, motor functions caudal to the spinal cord lesion are no longer used resulting in neuronal dysfunction. In contrast, in subjects with an incomplete SCI such training paradigms can lead to improved locomotor ability. Appropriate functional training involves the facilitation and assistance of stepping-like movements with the subjects' legs and body weight support as far as is required. In severely affected subjects standardized assisted locomotor training is provided by body weight supported treadmill training with leg movements either manually assisted or moved by a driven gait orthosis. Load- and hip-joint related afferent input is of crucial importance during locomotor training as it leads to appropriate leg muscle activation and thus increases the efficacy of the rehabilitative training. Successful recovery of locomotion after SCI relies on the ability of spinal locomotor circuitries to utilize specific multisensory information to generate a locomotor pattern. It seems that a critical combination of sensory cues is required to generate and improve locomotor patterns after SCI. In addition to functional locomotor training there are number of other promising experimental approaches, such as tonic epidural electrical or magnetic stimulation of the spinal cord, which both promote locomotor permissive states that lead to a coordinated locomotor output. Therefore, a combination of functional training and activation of spinal locomotor circuitries, for example by epidural/flexor reflex electrical stimulation or drug application (e.g. noradrenergic agonists), might constitute an effective strategy to promote neuroplasticity after SCI in the future.