Understanding the epidemiology of rare diseases is critically important to improving the diagnostic, therapeutic, and overall burden on individual patients, but also their families. Currently, there are approximately 8000 rare diseases in the world. There are various definitions used to define rare diseases, but generally a rare disease is defined as a disease with a prevalence of one case in 2000 individuals within a defined population. In addition, there is a wide variety of different types of rare diseases in both pediatric and adult cases including cancers as well as infectious, genetic, and metabolic diseases. From an epidemiological perspective, rare diseases pose some major methodological issues including finding an adequate sample size to conduct clinical trials, undertaking statistical analyses, and comparing cases based on the disease definition from various geographical regions of the world. Increased collaboration by medical researchers and the amazing coming together by the rare disease community have substantially improved the understanding of these diseases and the quality of life of affected persons, and thus ameliorated the impact these diseases have had on affected individuals and their families.