Traditionally, Mendelian (single gene) disorders have been categorized as ‘rare’ and considered ‘orphaned’ in more ways than one. In addition, diseases in emerging nations, that don’t affect developed nations, are called neglected diseases and are also victims of inattention. These distinctions, defined in legislation and policies in some nations, are not helpful in a number of ways – including for the affected individuals, the clinicians who serve them, the researchers trying to mitigate the effects of the disease and companies involved (or not). The intersection of biology and informatics, in the form of genomics integrated with clinical medicine, offers a pathway to a new world of collaboration toward the development of diagnostics and therapies for all diseases. In the dawning age of stratified medicine, all diseases are rare. It is time to join forces on multiple levels and create new paradigms for the solutions that will elude us if we continue to create orphans. We’ll consider the history of rare and neglected disease research and advocacy. We will also consider recent formation of the International Rare Disease Research Consortium and other efforts. Finally, we will consider the need for a collaborative effort using the long tail as a vehicle for citizens to create the revolution that is needed to radically accelerate disruptive strategies to provide insights to understanding and treating disease.