Julia-Lythgoe olefination (or simply Julia olefination) is an olefination process between phenyl sulfones and aldehydes (or ketones) to give alkenes after alcohol functionalization and reductive elimination using sodium amalgam or SmI2. It is mainly used to synthesize E-alkenes and is a key step in numerous total syntheses of many natural products. This review exclusively deals with the Julia-Lythgoe olefination and concentrates mainly on the applications of this reaction in natural product synthesis covering literature up to 2021.