In this article the role of Renshaw cell involvement in experimental amyotrophic lateral sclerosis (ALS) is discussed, with an emphasis on the anatomy, physiology, and possible role in motor control of Renshaw cells. These cells are located in lamina VII of the spinal cord, are excited by motor axon collaterals, and inhibit homonymous and synergistic motoneurons in a negative-feedback fashion (recurrent inhibition). Early dysfunction and/or loss of Renshaw cells has been suggested to occur in experimental ALS, and the hypothesis has been put forward that this may be the event that makes motoneurons more susceptible to glutamatergic toxicity in ALS. However, Renshaw cell properties and connectivity-in particular, the lack of recurrent inhibition in the more distal muscles of the limbs where, on the contrary, initial wasting is prominent in human ALS-make it unlikely that impairment of Renshaw cells is a general feature of the human form of the disease.