OBJECTIVE: Provide an up-to-date review for health care providers regarding clinically significant food-drug interactions and summarize recommendations for optimal medication administration in older adults and long-term care patients. DATA SOURCES: A literature search was performed using MEDLINE, PUBMED, and IPA abstracts to locate relevant articles published between January 1982 and July 2017. DAILYMED was used to identify manufacturer-specific medication administration recommendations. STUDY SELECTION AND DATA EXTRACTION: Articles were reviewed for inclusion based on their relevance to this subject matter and the integrity of the information provided. Additionally, the package labeling of included products was reviewed. DATA SYNTHESIS: The current recommendations for specific medication administration with regard to food are summarized descriptively. CONCLUSION: Clinically significant food-drug interactions are common and have been reported with multiple classes of medications. However, there are a limited number of studies examining food-drug interactions, and the majority of recommendations are made by product-specific manufacturers. Pharmacists should be aware of common food-drug interactions in the community, assisted living, long-term care, subacute care, and hospital settings. To optimize medication therapy and improve therapeutic outcomes, it is important for pharmacists and other health care providers to identify agents with potential for food-drug interactions and to understand the clinical relevance of such interactions.