St. John's wort (Hypericum perforatum) has been used as a medicinal herb for over 2000 years. Over the past 2 decades, its application as a plant extract for treating depression has undergone rigorous scientific investigation, and its effectiveness has been shown in studies comparing it with placebo and preference antidepressants. Safety and tolerability studies have revealed that St. John's wort (SJW) preparations have better safety and tolerability profiles than synthetic antidepressants. The indications for St. John's wort preparations comprise patients with mild or moderate depression. Based on the existing literature, limitations to efficacy in more severe cases as well as interactions and contraindications have to be respected.