The systematic study of drug metabolism began in the 19th Century but most of what we know now has been learned in the last 50 years. Drug metabolism continues to play a critical role in pharmaceutical development and clinical practice, as well as contributing to toxicology, chemical carcinogenesis, endocrinology, and drug abuse. The importance of the field will continue, but its nature will continue to develop with changes in analytical chemistry, structural biology, and artificial

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... . Challenges and opportunities include toxicology, defining roles of genetic variations, and application to clinical issues. Although the focus of this MiniReview is cytochrome P450, the same principles apply to other enzymes and transporters involved in drug metabolism. Significance Statement Progress in the field of drug metabolism over the past 50 years has helped make the pharmaceutical enterprise what it is today. Drug metabolism will continue to be important. Challenges and opportunities for the future are discussed.