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Explosions cause more complex and multiple forms of damage than any other wounding agent, are the leading cause of death on the battlefield, and are often used by terrorists. Because explosion-related injuries are infrequently seen in civilian practice, a broader base of knowledge is needed in the medical community to address acute needs of patients with explosion-related injuries and to broaden mitigation-focused research efforts. The objective of this review is to provide insight into the complexities of explosion-related injury to help more precisely target research efforts to the most pressing areas of need in primary prevention, mitigation, and consequence management.An understanding of the physics and biological consequences of explosions together with data on the nature or severity of contemporary combat injuries provide an empiric basis for a comprehensive and balanced portfolio of explosion-related research. Cited works were identified using MeSH terms as directed by subtopic. Uncited information was drawn from the authors’ surgical experience in Iraq, analysis of current combat trauma databases, and explosion-related research.Data from Iraq and Afghanistan confirm that survivable injuries from explosions are dominated by penetrating fragment wounds, substantiating longstanding and well-known blast physics mechanisms. Keeping this factual basis in mind will allow for appropriate vectoring of funds to increase understanding of this military and public health problem; address specific research and training needs; and improve mitigation strategies, tactics, and techniques for vehicles and personal protective equipment.A comprehensive approach to injury from explosions should include not only primary prevention, but also injury mitigation and consequence management. Recalibration of medical research focus will improve management of injuries from explosions, with profound implications in both civilian and military healthcare systems.