The risk for drug-drug interactions and related adverse side effects increases with the number of simultaneously administered drugs. This number, however, can often only marginally be limited particularly in elderly, multimorbid patients suggesting that the identification and prevention of drug-drug interactions is of pivotal interest within this group of patients. The spectrum of potential mechanisms that underlie pharmacokinetically relevant drug-drug interactions is rather narrow including processes of absorption, distribution, metabolism and excretion. Besides complexation and absorption processes during drug absorption, transport through membranes of the intestine, the liver, and the kidney, as well as enzymatic drug metabolism are the main processes that are involved in drug-drug interactions. Induction or inhibition of or competition for metabolizing enzymes or drug transporters by drugs, nutritional components or food may interfere with the pharmacokinetics of one or multiple drugs in a therapeutically relevant manner. To readily identify these drug-drug interactions, detailed knowledge is needed about the underlying mechanisms as well as the pharmacokinetic characteristics of each administered drug. The resulting measures to identify and prevent drug-drug interactions thus represent pivotal steps to improve drug therapy, to impede disease progression, and to increase the patients' quality of life.