Cancer is the second leading cause of death worldwide. There is thus increased interest in alternative treatment modalities that include chemotherapy, hormonal supplements, surgery, radiation therapy, complementary or alterative medicine, used alone or in combination. Therefore patients who are subjected to combination treatments such as hormonal supplements or alternative medicine face considerable risk of drug-drug interactions. The administration of herbal drugs by patients without a physician's prior counseling is increasing globally and there is a possibility of herb-drug interactions too. Herbal drugs or extracts themselves contain a combination of active constituents, which interact within themselves and also between other prescribed pharmaceutical drugs to either enhance (synergize) or decrease (antagonize) the therapeutic effect. This review focuses on a number of reports of herb-drug interactions, their mechanism of action with a special emphasis on dietetic phytochemicals such as quercetin, genistein, curcumin and catechins. All phytochemicals tend to increase the therapeutic effect by blocking one or more targets of the signal transduction pathway, by increasing the bioavailability of the other drug or, by stabilizing the other drug in the system. Copyright 2006 John Wiley & Sons, Ltd.