Amyotrophic lateral sclerosis (ALS) is the most common form of adult motor neuron disease. A brief overview of some of the more important genes identified in familial ALS is provided. To date, riluzole is the only drug that has demonstrated efficacy in patients with ALS. One of the most challenging aspects in translating candidate therapeutic agents for ALS to clinical use is the appropriate clinical trial design. ALS-relevant compounds has recently increased, and the potential for interfering RNA (RNAi) and antisense technologies to target a specific but well-characterized (mutant superoxide dismutase 1) protein responsible for many cases of familial ALS may offer proof of the principle that ALS can be effectively treated if the upstream causative etiologies are identified. Finally, recent advances in stem cell research, including the development of induced pluripotent stem cells, offer the potential for autologous cell transplantation as well as drug discovery.