The objectives of this chapter are threefold. First, we will define and discuss natural experiments in the context of chronic disease reduction and prevention. Natural experiment studies will be described in terms of the distinct opportunities and challenges of examining population-level or policy interventions implemented by community, government, and private-sector stakeholders. Second, we will discuss design and analysis methods to consider when conducting natural experiments. We will build on the STROBE (Strengthening the Reporting of Observation Studies in Epidemiology) and TREND (Transparent Reporting of Evaluations with Nonrandomized Designs) statements to help guide researchers conducting natural experiment studies. Finally, we will present real-world examples of natural experiments in Canada from our work. We will discuss the research and policy implications of our natural experiment studies and the challenges and opportunities they present.