The popularity of medicinal herbs has grown significantly in recent years despite a dearth of information regarding their modes of action and continuing concerns over their efficacy. Recent efforts to elucidate the mechanisms of action of several anti-inflammatory herbs have focused on a class of compounds, sesquiterpene lactones, that are believed to be the active components of these herbal medicines. Sesquiterpene lactones constitute a large and diverse group of biologically active plant constituents that have been reported from the Acanthaceae, Anacardiaceae, Apiaceae, Euphorbiaceae, Lauraceae, Magnoliaceae, Menispermaceae, Rutaceae, Winteraceae and the Hepatidae (liverworts). However, the greatest number has been reported from the Asteraceae. Tanacetum parthenium (feverfew) is one of the most prominent species in the Asteraceae and a known remedy for the treatment of various diseases. Feverfew has been used for at least two millennia for the treatment of fever, as well as headache, menstrual irregularities and stomach-ache. Today, feverfew is widely used as a migraine preventive, and more recently as an aid for those suffering from arthritis and inflammation. The drug feverfew contains a series of compounds, particularly sesquiterpene lactones, which, being parthenolide, are regarded as the main cause of the therapeutic properties of the plant. Although a few studies have been published which evaluate the effects of parthenolide in vivo, several studies have been undertaken to investigate the molecular basis of the pharmacological effect of parthenolide. This review will summarize some of the most important reports on the role of parthenolide in intracellular signalling processes from the literature data (2004-2007).