In the early fall of 1897, yellow fever shuttered businesses, paralyzed trade, and caused tens of thousands of people living in the southern United States to abandon their homes and flee for their lives. Originating in Cuba, the deadly plague inspired disease-control measures that not only protected U.S. trade interests, but also justified the political and economic domination of the island nation from which the pestilence came. By focusing on yellow fever, this book uncovers for the first time how the devastating power of this virus profoundly shaped the relationship between the two countries. It demonstrates that yellow fever in Cuba motivated the United States to declare war against Spain in 1898, and, after the war was won and the disease eradicated, the United States demanded that Cuba pledge in its new constitution to maintain the sanitation standards established during the occupation. By situating the history of the fight against yellow fever within its political, military, and economic context, the book reveals that the U.S. program of sanitation and disease control in Cuba was not a charitable endeavor. Instead, it shows that it was an exercise in colonial public health that served to eliminate threats to the continued expansion of U.S. influence in the world.