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Several species of the genus Tanacetum L. (Asteraceae) spread in the Southestern Europe are traditionally used as medicinal and aromatic plants, including T. vulgare, T. parthenium, T. macrophyllum, T. balsamita, T. poteriifolium. The review is focused on the phytochemical and pharmacological studies of these taxa. Major chemical constituents are acylquinic acids, sesquiterpenes, sesquiterpene lactones, methoxylated flavonoids. An in-depth depiction of more than 100 secondary metabolites was achieved in Tanacetum species by liquid chromatography-high resolution mass spectrometry. The ethnopharmacological studies indicate that species possess antioxidant, enzyme inhibitory and cytotoxic activity along with antimicrobial and antiviral effects. Reports revealed anti-inflamatory and neuromodulatory activity involved in the pharmacological approach in counteracting migraine attacks. Multivariate data analysis allowed the identification of the most discriminant metabolites and bioactivities in the herbal drugs. This review emphasizes T. vulgare, T. macrophyllum, T. balsamita and T. parthenium as potential raw material for health-promoting application in pharmaceutical area.