Sesquiterpene lactones (SL) group, comprises more than 6000 compounds, with high biological potential. Access to SL biological potential could be achieved by solid-liquid extraction, with solvent and extraction process as key factors for a successful extraction. SL research has been mainly focused on compounds identification, with a large range of solvents being applied, not all corresponding to the European Medicines Agency guidelines, using different conventional extraction methodologies. Moreover, there is still a lack of scientific knowledge regarding the extraction solvent and methodology effect upon SL extraction from plants, and its bioactivity, towards final applications. This review aims to provide a perspective regarding the impact of extraction solvents and method-ologies upon SL extraction efficiency, as well as the purification methods applied till date, highlighting the overall impact on final extraction efficiency, underlying pertinent aspects for future economic valorization opportunities, as well research challenges towards industrial applications regarding SL plants extraction. & COPY; 2022 Elsevier B.V. All rights reserved.