Until the last half of the 20th century, infectious diseases dominated the health profile of northern North American Aboriginal communities. Research on the 1918 influenza pandemic exemplifies some of the ways in which the social context of European contact and ensuing economic developments affected the nature of infectious disease ecology as well as the frequency and severity of the problem. To understand these impacts it is necessary to consider the web of interactions among multiple pathogens, the biology of the human host, and the social environment in which people lived. At the very least, an understanding of the history of the impact of infectious diseases on northern North American communities requires attention not only to potential interactions among cocirculating pathogens, but their links to key social, historical, and economic factors that exacerbated their adverse effects and contributed to excess mortality.