St. John's wort is an herb commonly used in Europe for decades and more recently the topic of scientific investigation in this country. St. John's wort has been found more effective than placebo and equally as effective as tricyclic antidepressants in the short-term management of mild-to-moderate depression. Comparisons to selective serotonin reuptake inhibitors have provided equivocal data. While it is generally well tolerated in clinical use, there is accumulating evidence of significant interactions with drugs. This evidence-based presentation of the literature includes a brief description of pharmacodynamics and clinical applications, followed by a systematic review of adverse effects, toxicity, and drug interactions.