This introductory chapter considers the role of disease—and in particular leprosy—on Hawaiian history. Biological exchange has always been a consequence of people's interactions with one another. Subsequently, the biological exchange of disease has also influenced the history of human communities—politically, economically, socially, and culturally. The Hawaiian case is no different, although the chapter observes some scholarly neglect in this phase of Hawaiian history, and aims to add another layer of understanding to the known history of Hansen's disease (leprosy) and infectious disease in Hawaiʻi. This chapter, and the book in general, attempts to approach the history of leprosy in the context of environment, experience, and culture—which not only share a reciprocal relationship, but which also help to define concepts of health, disease, and medicine for any society.