Neural networks in the spinal cord, referred to as "central pattern generators" (CPGs), are capable of producing rhythmic movements, such as swimming, walking, and hopping, even when isolated from the brain and sensory inputs. This article reviews the evidence for CPGs governing locomotion and addresses other factors, including supraspinal, sensory, and neuromodulatory influences, that interact with CPGs to shape the final motor output. Supraspinal inputs play a major role not only in initiating locomotion but also in adapting the locomotor pattern to environmental and motivational conditions. Sensory afferents involved in muscle and cutaneous reflexes have important regulatory functions in preserving balance and ensuring stable phase transitions in the locomotor cycle. Neuromodulators evoke changes in cellular and synaptic properties of CPG neurons, conferring flexibility to CPG circuits. Briefly addressed is the interaction of CPG networks to produce intersegmental coordination for locomotion. Evidence for CPGs in humans is reviewed, and although a comprehensive clinical review is not an objective, examples are provided of animal and human studies that apply knowledge of CPG mechanisms to improve locomotion. The final section deals with future directions in CPG research.