The cytochromes P-450 recognize and metabolize a broad range of structurally diverse therapeutic agents. As a consequence, many clinically relevant drug-drug interactions (DDI) are associated with inhibition and/or induction of a specific P-450 enzymes (in particular human cytochrome P-450 3A4, CYP3A4). In addition to inhibition and induction, CYP-mediated drug metabolism may be enhanced upon coincubation with certain compounds. Moreover, some of these enzyme-based interactions appear to be substrate specific. In this presentation, several issues associated with the generation of accurate DDI information will be discussed.