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Herbal medicines including traditional Chinese medicine are becoming increasingly more popular worldwide. However, there is considerable potential for interaction between herbal components and drugs, as all herbal medicines contain a combination of potentially biologically active compounds possessing various inherent pharmacological activities, and the components of herbal products consumed are eliminated from the body by the same mechanisms that remove drugs. Indeed, many so-called conventional drugs are derived from plant sources. This article provides an update on the mechanisms and evidence of drug–herb interactions (DHIs) and genetic influences on DHIs. The rational prediction of clinically important DHIs is also discussed. Individualized and targeted drug therapy could be achieved by identifying the population most likely to be helped or harmed by drug–herb coadministration.