This chapter relates the history of sugar, a thread that links the Silk Roads, Portuguese sailors, Atlantic islands, endangered seals, the African slave trade, and yellow fever, all because of our physiological need for glucose, which we satisfy with sugar. The chapter tells how from its origin in Southeast Asia, sugarcane, later called “Creole cane” and processing technology moved along the Silk Roads to Western Asia, then to Mediterranean islands. To begin with, Portuguese colonists transformed the Atlantic island of Madeira into a large sugar producer using slave labor until ecological and economic collapse forced production to move to São Tomé, using Angolan slave labor. After Portugal discovered Brazil, colonists took sugarcane with them, creating large plantations and initiating the enslavement and trans-Atlantic movement of millions of Africans. As the chapter shows, sugar production moved into the Caribbean and Central America, and African slave ships inadvertently carried yellow fever and yellow fever mosquito to the Americas.