In recent years, public and scientific interest in plant flavonoids has tremendously increased due to postulated health benefits. Whereas the amount of flavonoids ingested with the regular diet is rather low, the use of supplements enriched with these polyphenolics is becoming increasingly popular. This raises concerns about possible interactions of flavonoids with therapeutic drugs, because both are xenobiotics and, thus, share at least partially the same metabolic pathways. A number of in vitro studies have shown effects of flavonoids on enzymes involved in xenobiotic metabolism, like cytochrome P450 monooxygenases and phase II conjugation enzymes, or on membrane transporters involved in drug excretion. Several investigations have also reported changes of drug bioavailability by certain flavonoids. This article attempts to present an overview of flavonoid effects on pathways involved in drug metabolism. It focuses on phase I and phase II enzymes as well as on transporters involved in drug metabolism which are expressed in the gastrointestinal tract.