In recent years, there has been a globally increasing application of herbal medicines and dietary supplements to treat various chronic diseases and to promote health. However, there are increasing clinical reports on the organ toxicities associated with consumption of herbal medicines. In general, most xenobiotics are metabolized by Phase I reaction(the main enzyme : cytochrome P450) and Phase II reaction. However, reactive oxygen species, free radicals and electrophils are produced inevitably during xenobiotics metabolism. These toxic species and metabolites are increased whenever the endogenous substances and enzymes for Phase II reaction not available. In addition, herbal-drug interactions are pharmacokinetic, with most actually or theoretically affecting the metabolism of the affected product by way of the cytochrome P450 enzymes. This review updated the knowledge on metabolic activation of herbal components and its clinical and toxicological implications. Also, the possible way for preventing the side-effects by herbal-medicine use was suggested.