Esculetin is the main active ingredient of Cortex Fraxini, its chemical name is 6,7-dihydroxycoumarin. This review covered recent studies on the synthesis, pharmacological activities and mechanism of esculetin and its derivatives over the past decade. With a variety of novel esculetin derivatives being continuously synthesized, the development and clinical application of Cortex Fraxini and its main ingredient esculetin will be more prospective.