One of the remarkable and unique aspects of the recent history of rare disease research has been the evolving role of patient advocacy groups and the collaborative partnership that exists among such groups and the scientists who study rare diseases, as well as the government officials charged with overseeing medical research and regulatory processes. This collaboration, which in many respects developed out of necessity on all sides, is unparalleled in other areas of medical research and product development. It has played a significant role over the past 30 years in the adoption of public policies, available research funding and other factors affecting the general climate for research on rare diseases. Specific areas of interest include the adoption of the Orphan Drug Act in the U.S. in 1983 and subsequent similar legislation elsewhere in the world; the relationship of patient advocacy groups with government research funding and regulatory entities; the role of patient advocacy groups in seeking to "de-risk" orphan product development through initiatives such as facilitating patient registries and disease natural histories; the role of advocacy groups in ensuring that patients have access to treatments; and the increasing globalization of patient advocacy initiatives.