Sulfur mustard (SM) is a bifunctional alkylating agent that can react with multiple biochemical molecules such as DNA, RNA, proteins, and so on, and its alkylation with DNA is one of the major poisoning mechanisms. Presently the pathogenesis of SM included DNA alkylation, poly ADP-ribose polymerase (PARP) activation, oxidative stress, inflammation, activation of immunoregulation and proteolytic enzymes, etc. By now there have been no specific antidotes in clinical treatment, and all the existing drugs are mainly used for symptomatic treatment. The drugs used clinically and currently being under development include free radical scavengers, antioxidant agents, PARP inhibitors, anti-inflammatory drugs and protease inhibitors. This review summarized the advances in pathogenesis of SM and the corresponding protective drugs.