Abstract: Covalent inhibitors bind to target proteins through covalent bonds, and further inhibit them. Researchers have been discouraged by covalent inhibitors because of their potential long-term off-target effect. However, with the in-depth study and exploration of the mechanism of covalent inhibitors, the character of electrophilic warhead and nucleophilic amino acids as well as the implementation and improvement of effective development strategies in recent years, many covalent inhibitors have been successfully approved. Their advantages in the treatment of diseases have gradually emerged, making covalent inhibitors a hot spot in drug development. This review focuses on the binding mechanism, research progress, development strategies, advantages and challenges of covalent inhibitors, and discusses their development prospect and direction, in the hope of providing some reference for the development of novel covalent inhibitors.