Vesicating agents continue to remain a likely threat as weapons of warfare or terrorism. The skin, eyes and lungs are particularly sensitive to vesicating agents (e.g. sulfur mustard (HD)) and their complications. Currently there are no specific medical countermeasures or treatment regimens for vesicating agents. In addition, there are no animal models that exactly mimic the development of HD injury. One of the most unique challenges in developing a chemical warfare medical countermeasure like an antivesicant is that data must be extrapolated to man from animal efficacy testing since exposure studies cannot be performed in humans. Ideally an animal model should be 1.) readily available, cost effective and amenable to vesicant exposure and drug testing; 2.) as physiologically and anatomically close as possible to humans, mimicking symptoms of vesicant exposure as seen in humans; 3.) versatile enough to be applicable to one or potentially several scenarios being tested, and finally 4.) capable of yielding readily reproducible results and have a large database that is accepted in the research and regulatory communities. Over the past several years a number of laboratories in the U.S. and other countries have developed animal models to evaluate pretreatment and treatment countermeasures. In the area of cutaneous skin injury, the mouse ear vesicant model, rabbit ear, hairless guinea pig, nude mouse and porcine models are actively being used by many laboratories. These models have been used to evaluate anti-inflammatory drugs, scavengers, protease inhibitors and poly (ADP-ribose) polymerase modulators. In the area of ocular research the rabbit eye model is the most widely used injury model. Promising candidates for ocular treatments to vesicant exposure include predominantly combination therapies (e.g. steroids, anti-inflammatory, and/or antiproteases). Many of these models have become well established and recognized as leading to significant advancement of our knowledge on efficacy of candidate compounds, and confirmation of in vitro test results and as elucidating the mechanism of action of HD injury. In conclusion, animal models continue to play an important role and are currently the only means by which antivesicants can be tested and results extrapolated to humans. A large database has been compiled from these preclinical studies using these models and will be summarized in this presentation.