Abstract: Covalently modified drugs, which exert their pharmacological effects by covalently binding to the targets, have been avoided as far as possible for a long time in drug design due to the potential off-target effects and other side-effects. With the in-depth study of binding modes of market blockbuster covalent drugs, more and more attention has been concentrated on covalently modified drugs. Current challenges remain in development of potent selective covalently modified drugs with fewer adverse effects. This paper reviews the classification of some covalently modified drugs, the drug-target binding modes and the new strategies of designing covalently modified drugs, in order to provide reference for rational design of covalent drugs.