Natural health products (or dietary supplements) refer to those products found in oral dosage forms, containing 1 or more active ingredients considered to be a nutrient, an herbal product, or any other nonnutrient/nonherbal substance. Their use continues to increase in the general population and in patients seen by nutrition support clinicians. Aside from an appraisal of product safety and effectiveness, attention should be paid to the potential for these product ingredients to interact with medication. Estimates are that at least 15 million adults in the United States are at risk for supplement-drug interactions. These can occur through both pharmacokinetic and pharmacodynamic mechanisms. This review describes the influence of dietary supplements on both the disposition and the effect of medication and provides numerous examples. Patients at greatest risk for interactions are those with chronic disease, who use multiple medications-particularly those with a narrow therapeutic range-have genetic variants in drug metabolism, impaired organ function, and are at either end of the age spectrum. Knowledge of the specific effects on drug absorption, metabolism, and effect is still incomplete. Relative to the large number of possible interactions between supplements and medication, only a small number of combinations have been examined or reported. The greatest limiting factor remains the quality or reliability of the existing evidence, as many widely accepted interactions are only theoretical based either on in vitro data or known pharmacology. A distinction needs to be clearly drawn between "documented" interactions and "potential" interactions. Although drug-drug interactions have been widely recognized, supplement-drug interactions may be as important to recognize, report, and manage.