It has been known for almost a century that caloric restriction can extend the life span of rodents and many other types of animals. Approximately 25 years ago, it was found that a methionine-restricted (MR) diet could replace a caloric-restricted diet with the result of extending the life span of animals. This chapter summarizes the effects of MR on the reversal of diabetes, obesity, and other aspects of the metabolic syndrome, as well as extending the normal life span. The most effective way to restrict methionine in the body, using orally-delivered methioninase, is also explored.