As a general rule, the use of medication increases considerably with advancing years. In many cases, the elderly are using drugs for chronic and degenerative disease for longer periods of time. Polypharmacy, the combined use of several drugs, is generally regarded as a high risk, especially in a population that is already at risk because of various other factors. Not surprisingly, adverse drug reactions are a major problem in elderly persons and a common cause of admission to hospital. Compared to drug–drug interactions, the possible effects of food on drug actions or side-effects or, vice versa, the effects of drug use on (micro-)nutrient status are receiving far less attention. Drug-nutrient interactions can be bi-directional. The vast majority of the literature concentrates on the general mechanisms of food effects on drugs. By contrast, much less is known on the effects of drugs on micronutrient uptake, storage or elimination. Effects of medication on nutrient status are easily overlooked, as they generally develop slowly and may go together with other social, nutritional, clinical and other changes. It seems conceivable that drug-induced nutrient deficiencies are relatively more frequent in the elderly than in younger patients. This chapter discusses the most important examples and mechanisms of drug-nutrient interactions. Attention is also paid to general age-related changes in drug effects. In the elderly, dietary habits may change, food intake tends to decrease and requirements of macro- and micronutrients may be different. The use of medicinal preparations, including OTC products and food supplements is on average very high in the elderly population. The sparse systematic information that is available on drug-induced changes in nutrient status, for example B12 and D, is often limited to studies in younger people and comprise one drug at a time. It seems highly conceivable that drug-nutrient interactions are under-diagnosed in the elderly population and that there may be much more under the water line. This will be particularly true for specific groups such as frail elderly persons taking several drugs at a time, or persons having a low dietary intake. Health care professionals should be aware that an elderly person’s new symptoms can be attributable to an underlying drug–nutrient interaction.