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Objective: Prescription drug use is on the rise, and the use of dietary supplementation remains common. In the United States, more than half of all adults take a dietary supplement in any given month. As a result, drug-nutrient interactions are becoming an important consideration when pharmacists counsel patients about their drug regimens. We reviewed the literature to identify common and/or clinically relevant drug-nutrient interactions that pharmacists may encounter in practice. Data Sources: A MEDLINE search for English-language publications from 1970 through March 2017 was performed using search terms (and variations) related to drugs, medications, micronutrients, and interactions. Study Selection and Data Extraction: Relevant studies, case reports, and reviews describing drug-nutrient interactions were selected for inclusion. Data Synthesis: Some drug-nutrient interactions may result in micronutrient insufficiencies or even frank deficiencies, thereby necessitating augmentation with multivitamin/minerals or individual vitamin/mineral dietary supplements. This most often occurs with long-term therapy for chronic conditions, such as treatment with proton-pump inhibitors and histamine-2 receptor antagonists. In addition, some chronic diseases themselves, such as diabetes, may predispose patients to micronutrient insufficiencies, and dietary supplementation may be advisable. Conclusions: Drug-nutrient interactions can often be resolved through specific dosing strategies to ensure that the full effect of the medication or the dietary supplement is not compromised by the other. In rare cases, the dietary supplement may need to be discontinued or monitored during treatment. Pharmacists are in a key position to identify and discuss these drug-nutrient interactions with patients and the health care team.