Epidemiology can be broadly defined as the study of the cause and distribution of diseases in human populations. This review is concerned with the role of epidemiology in elucidating the cause of insulin-dependent diabetes mellitus (IDDM). Methodological aspects of epidemiologic studies are discussed including study designs and their limitations. Markers of genetic susceptibility to IDDM are examined in terms of their potential value for selecting high risk individuals for prospective follow-up studies of IDDM etiology. Models of disease causation pertinent to IDDM are presented with a primary focus on the recently developed epigenesis theory. Finally, a framework is provided that integrates approaches of infectious disease, chronic disease and genetic epidemiology, to link epidemiologic data with information from other disciplines, such as genetics, microbiology or immunology.