St. John’s wort was traditionally used for fatigue, and associated anxiety and depressive symptoms, and also for neurasthenic (nerve weakness) conditions internally, and for wound healing externally. The name hypericum is thought to be derived from the Greek words, ‘hyper’ and ‘eikon’, meaning ‘to overcome an apparition’; it had a reputation in ancient times for ‘warding off evil spirits’. The vast proportion of research in more recent times has focused on use in depression. Clinical studies have shown that St. John’s wort is an effective treatment in cases of mild to moderate depression, comparable with and better tolerated than conventional antidepressants. Its role as an antiviral has been explored, mainly in laboratory studies. Interaction issues are at the forefront of any discussion regarding St. John’s wort. Use is contraindicated in patients taking immunosuppressant drugs (cyclosporin, tacrolimus), HIV drugs (nonnucleoside reverse transcriptase inhibitors and protease inhibitors), chemotherapeutic drugs (irinotecan, imatinib), anticoagulants (warfarin, phenprocoumon) and the cardiac glycoside digoxin (at doses of more than 1g per day). Caution needs to be applied when considering co-medication with a range of other medications. St. John’s wort has become an extremely popular herbal medicine and consequently been taken by a very large population around the world. Published cases of serious adverse events are very low considering the extent of use. St. John’s wort can be considered a safe herb if used carefully.