Amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of motor neurons, but the disease also seems to involve glial cells such as oligodendrocytes and their precursors. Kang et al. now show that there is extensive degeneration of grey matter oligodendrocytes in the spinal cord of the superoxide dismutase 1 (SOD1) mouse model of ALS; although there is also increased proliferation and differentiation of oligodendrocyte precursors, these cells fail to mature into functioning oligodendrocytes. Selective removal of the mutant gene from oligodendrocytes in these mice delayed the progression of the disease, indicating that the genetic defect in ALS might cause motor neurons to degenerate by reducing the ability of oligodendrocytes to support them.