People mistakenly think that all herbs are safe, because of the fact that they are natural, and the use of herbal medication is growing. Aspects of the efficacy, safety, and quality of herbal or natural products are the subjects of on-going debates. Concurrent administration of herbs may interfere with the effect of drugs. Lack of knowledge of the interaction potential together with an underreporting of herbal use poses a challenge for health care providers and a safety concern for patients. A good understanding of the mechanisms of herb-drug interactions is also essential for assessing and minimizing clinical risks. Examples of herbal medicine-pharmaceutical drug interactions of commonly used herbs are presented. The potential pharmacokinetic and pharmacodynamic basis of such interactions is discussed, as well as the challenges associated with the identification and prediction of herb-drug interactions.