Drug-drug interactions (DDI) represent a serious concern for physicians, patients, and researchers involved in the discovery and development of new drugs. In most cases, interactions arise via a significant change in the exposure of one drug (the “victim”) caused by a second drug (the “perpetrator”). The perpetrator drug elicits such effects via inhibition or induction of enzymes involved in drug metabolism, although more recently effects on drug transporters have also been demonstrated. With our understanding of drug metabolizing enzymes, these in vivo phenomena can now be predicted using in vitro approaches; in vitro enzyme kinetic experiments can be considered as an analogue to in vivo pharmacokinetics. The purpose of this presentation is to lay out the concept of drug clearance as it relates to pharmacokinetics and pharmacokinetic-based DDI, such that the participant can fully understand the subsequent presentations on the experimental approaches used to predict human DDI.