Until reports of interactions between St John's wort and drugs such as digoxin, warfarin, protease inhibitors and oral contraceptives began to appear, very few herb-drug interactions were documented. These are now becoming more common, although still rare compared with drug-drug interactions. In the absence of hard data, potential interactions are being highlighted, and this review attempts to distinguish between the speculative and the proven. The subject is approached from a therapeutic point of view since in most cases the patient is already taking one or more prescription drugs, and the question is whether or not it is safe for a particular herb to be added to the regimen. Although many of the examples of herb-drug interactions are minor or theoretical at present, the fact remains that some are serious and life threatening, and these almost exclusively concern cyclosporin, anticoagulants, digoxin, antidepressants and protease inhibitors, taken with the herb St John's wort. Ginkgo and ginseng are implicated in a number of reports, but many of these are unsubstantiated. To date, the cardiovascular, central nervous and immune systems are the most common therapeutic categories cited in the literature and other than those, examples are very limited. Although many herbal drugs have good safety profiles, it must be borne in mind that herbal supplements are intended to be taken over an extended period of time, which provides the opportunity for enzyme induction and other mechanisms of interaction to take effect.