Infection and inflammation are associated with down-regulations of hepatic and extrahepatic cytochrome P450s, as well as other drug metabolizing enzymes and transporters. We will review the genesis of inflammatory reactions, and discuss the relevance of the inflammatory regulation of P450 enzymes observations to clinical drug-disease and drug-drug interactions. Mechanistically, understanding the enzyme specificity and mechanisms of regulation will allow us to make better decisions about drug dosage regimens when a patient’s inflammatory status changes.