A natural experiment is an empirical study in which individuals (or clusters of individuals) exposed to the experimental and control conditions are determined by nature or by other factors outside the control of the investigators, yet the process governing the exposures arguably resembles random assignment. Thus, natural experiments are observational studies and are not controlled in the traditional sense of a randomized experiment. Natural experiments are most useful when there has been a clearly defined exposure involving a well defined subpopulation (and the absence of exposure in a similar subpopulation) such that changes in outcomes may be plausibly attributed to the exposure. In this sense the difference between a natural experiment and a non-experimental observational study is that the former includes a comparison of conditions that pave the way for causal inference, while the latter does not. Natural experiments are employed as study designs when controlled experimentation is extremely difficult to implement or unethical, such as in several research areas addressed by epidemiology (e.g., evaluating the health impact of varying degrees of exposure to ionizing radiation in people living near Hiroshima at the time of the atomic blast) and economics (e.g., estimating the economic return on amount of schooling in US adults).