For the past ten years the US Army Medical Research and Materiel Command (USAMRMC) has directed a basic and applied research program aimed at identifying a medical countermeasure against vesicant agents. The emphasis of this program has been a medical protection against sulfur mustard and its cutaneous pathology--blister formation. The driving forces of this program have been an Army Science and Technology Objective (STO) and two Defense Technology Objectives (DTO). Through the efforts of an extensive intramural and extramural research network centered at the US Army Medical Research Institute of Chemical Defense (USAMRICD), all the goals of the STO and DTOs have been met. This review will define the pharmacological strategies investigated and focus on the two strategies selected for transition to advanced development, i.e., anti-inflammatories and chemical scavengers. We will also review the expansion of our understanding of the pathophysiological mechanisms of mustard injury that has come from this research. Also, we will discuss the future directions for those products from this program. While great strides have been made through these investigations, the complexity of the mustard insult demands that further studies extend the inroads made and points the way to better understanding of cellular and tissue disruptions caused by sulfur mustard.