Locomotor disorders profoundly impact quality of life of patients with spinal cord injury. Understanding the neuronal networks responsible for locomotion remains a major challenge for neuroscientists and a fundamental prerequisite to overcome motor deficits. Although neuronal circuitry governing swimming activities in lower vertebrates has been studied in great details, determinants of walking activities in mammals remain elusive. The manuscript reviews some of the principles relevant to the functional organization of the mammalian locomotor network and mainly focuses on mechanisms involved in rhythmogenesis. Based on recent publications supplemented with new experimental data, the authors will specifically discuss a new working hypothesis in which pacemakers, cells characterized by inherent oscillatory properties, might be functionally integrated in the locomotor network in mammals.