The natural history of a disease is traditionally defined as the course a disease takes in the absence of intervention in individuals with the disease, from the disease’s onset until either the disease’s resolution or the individual’s death. A natural history study is a preplanned observational study intended to track the course of the disease. Its purpose is to identify demographic, genetic, environmental, and other variables (e.g., treatment modalities, concomitant medications) that correlate with the disease’s development and outcomes. Natural history studies are likely to include patients receiving the current standard of care and/oremergent care, which may alter some manifestations of the disease. Disease registries are a frequent platform to acquire the data for natural history studies. Knowledge of a disease’s natural history is important for planning drug development; however, there is only limited information about the natural history of most rare diseases.