In the late fifteenth century, a handful of small European states began to refashion the world. Prior to that time, most of the world’s wealth had been located in Asia, the Middle East, and the Indian subcontinent, where traditional trade networks in luxury items, from spices to slaves, enriched the sultans and emperors of the grand Asiatic empires. With two striking maritime voyages, however, Europe entered the age of discovery and, eventually, the age of colonialism. These voyages explain how Europeans ascended to a position of global domination through command of resources such as silver and sugar, and exchange of such micro-organisms as the smallpox virus. Between the fifteenth and the nineteenth centuries, once-great empires and civilizations crumbled under the pressure of Eurasian microbes, military technologies, colonial rule, and economic rapaciousness. The early modern age witnessed the dispersal of European culture and institutions globally, including to the shores of Japan. Japan survived Europe’s age of discovery, however, and did so completely intact, at least compared to the New World, India, and China, for reasons that will be described in this chapter. Importantly, Japan’s initial encounter with Europe in the sixteenth century contributed to its relative successes against later Western imperialism in the nineteenth.