Herpes simplex viruses (HSV-1 and HSV-2) are responsible for long-term latent infections in humans, with periods of recurring viral replication associated to lesions around the lips, eyes, mucous membrane of the oral cavity or the genitals. The lack of an effective vaccine, the moderate to high toxicity of the available synthetic antiherpes compounds and the appearance of resistant viral strains emphasize the need for new inhibitors. Tanacetum vulgare, commonly known as tansy, has been used for treating rheumatic pain, skin eruption and diuretic conditions as well as an anthelmintic, antihypertensive, stimulant, emmenagogue, carminative, antiseptic, antihypertensive, antispasmodic and antioxidant agent. The anti HSV-1 activity of tansy aerial parts, ethyl acetate extract and the isolated compound parthenolide, has been reported recently. In this work, through a comprehensive mechanistic-based antiherpetic activity study, it was revealed that constituents other than parthenolide are responsible for the antiviral activity of tansy. Copyright © 2010 John Wiley & Sons, Ltd.