Since publication of the last edition, our understanding and treatment of ALS have changed dramatically. The many puzzles of this disease are being steadily solved. A number of causes of familial ALS have been identified, and the mechanisms of motor neuron cell death are much better understood. The FDA approved riluzole in 1996 as the first drug ever approved for the treatment of ALS. Although expected for the past dozen years, it is frustrating to say that additional drugs have not been developed. Yet, new drugs continue to be tested and others are on the horizon.