Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized primarily by motor neuron loss in the motor cortex and spinal cord leading to progressive disability and death. Despite the relative selectivity of motor neuron loss, recent studies have implicated other cell types including astrocytes and microglia as contributors to this cell death. This understanding has resulted in stem-cell-replacement strategies of these cell types, which may result in neuroprotection. In addition to cell-replacement strategies, the development of induced pluripotent stem cell (iPSC) technologies has resulted in the establishment of motor neuron cell lines from patients with ALS. The use of iPSCs from ALS patients will allow for potential autologous cell transplantation, drug discovery, and an increased understanding of ALS pathobiology.