Abstract: Proteolytic targeting chimera (PROTAC) technique is an newly-emerging strategy to chemically induce the target protein degradation by the ubiquitin-proteasome pathway. PROTAC is a bifunctional molecule that consists of a target protein ligand, a linker and an E3 ligase ligand, which can simultaneously recruit target protein and E3 ligase, ultimately leading to the target protein degradation. The promising application and development of PROTAC has been rapidly gaining the momentum in the field of drug discovery. The present review gives an overview of PROTAC, with respect to the mechanism of action, development history, as well as the opportunities and challenges in the discovery of small-molecule drugs.