This chapter reviews the role of expanding sugarcane plantations throughout the Caribbean in the movement of slaves, mosquitoes and disease, as world empires jockeyed for dominance in world sugar markets. It relates how increased sugarcane production and exports to Europe led to increased importation of slaves to work the fields. As the African embarkation point of slaves moved north to the Slave Coast, yellow fever and the mosquito Aedes aegypti came into play, though when England banned slaveholding, sugar production shifted to the Spanish colonies of Puerto Rico and Cuba. The brief Spanish-American War of 1898, over control of Cuba, cemented the fame of Colonel Theodore Roosevelt but resulted in more deaths from yellow fever than combat, with the outbreak continuing during the post-war occupation of Cuba. Serendipity played a significant role in the subsequent discovery of the cause of the disease, connecting the Yellow Fever Commission, led by Major Walter Reed, with Cuban physician, Dr. Carlos Finlay, whose early experiments pointed to mosquitos and others while a series of experiments by Reed's team showed Aedes aegypti was the vector.