Coffee, right after water and tea, is the third most commonly consumed beverage in the world. Coffee contains over 1000 chemical compounds, the most well-known of which are caffeine, chlorogenic acid, caffeic acid, ferulic acid, etc. Such a large composition of various chemical substances present in coffee creates the possibility of certain interactions with drugs. Interactions between beverages and drugs may inadvertently reduce or increase the drug effect. From a clinical point of view, it is important to know whether there are situations when it is necessary to limit coffee consumption (or maintain a certain time interval after taking medications). In order to reduce the risk of potential interactions (as well as side effects), large amounts of caffeine should be avoided. Most of the interactions described between coffee and medications are of no clinical significance. However, it should be remembered that in some specifically genetically determined people, such an interaction may have a much stronger clinical face. This chapter summarizes information on the interactions of coffee (mainly caffeine) with drugs.