This chapter describes the emergence of the category of rare diseases. This category first appeared in the 1960s in the USA as a means to solve the orphan drug problem. At that time, orphan drugs were existing drugs that had to be withdrawn from the American market following an amendment of 1962 to the Food, Drug and Cosmetics Act. As a result, some patients were deprived from their treatment. The Food and Drug Administration (FDA) organized meetings with the stakeholders to find a solution, and thus gave patients with a rare disease an opportunity to make sense of their illness experience. The meetings led to the Orphan Drug Act, which defines orphan drugs as drugs intended for rare diseases. In the European Union, a slightly different sequence of actions led to the adoption in 1999 of the Regulation on Orphan Medicinal Products and to patients mobilizing in order to have rare diseases considered a public health issue.