The therapeutic effects of many herbal medicines have been well established; however, definitive mechanisms of action remain to be elucidated for many psychoactive herbal medications. Although several mechanisms have been identified, they are often insufficient to account for the observed effects of the plant or its extracts. This review emphasizes that, in addition to searching for more potent mechanisms, one must consider the additive and supra-additive effects of a plant's multiple constituents. Synergy may occur through pharmacokinetic and/or pharmacodynamic interactions. Examples are given that illustrate synergistic actions in St. John's wort (Hypericum perforatum), kava kava (Piper methysticum), and valerian (Valeriana officinalis).