More so than any other infectious disease, malaria has all too often affected the conduct of military operations in war and in some cases has disproportionately influenced the outcome. From Napoleon's defensive action at Walcheren, to the Union Army's attempts to take control of the Mississippi River at Corinth and Vicksburg, to the dreadful numbers of malaria casualties suffered by U.S. Marines on the islands of Efate and Guadalcanal during World War II and more recently in Liberia in 2003, malaria has extracted a heavy toll. In this article, we summarize a few of the significant contributions to malaria control by U.S. military personnel throughout its history. We review examples of scientific achievements, medical breakthroughs, and lessons learned from preceding wars that continue to drive the quest for effective antimalarial therapies and preventive vaccines. This review is by no means comprehensive or complete but serves as a testament to the skill, courage, self-sacrifice, and devotion to duty of the many who have faithfully served their country in the past and to those today who continue the struggle against this disease.