Approximately 59% of all spinal injuries are incomplete, leaving spared pathways capable of plasticity. While spontaneous plasticity partially restores walking ability, it seldom enables return to functional, overground walking. Acute intermittent hypoxia (AIH) is a novel, noninvasive means to induce spinal plasticity, strengthening spared pathways to motoneurons after iSCI. Hypoxia in rodents activates carotid chemoafferents that stimulate serotonin, which triggers synthesis of brain-derived neurotrophic factor (BDNF) and activation of TrkB, enhancing synaptic input and motor output of respiratory and somatic motor nuclei. In humans with iSCI, hypoxia increases ankle strength.