The article summarizes the world experience in helping patients with rare diseases, the history of the development of “orphan” medicine, reviews foreign strategies and the fundamental documents that form the modern foreign models of care for patients with orphan diseases. The problems of providing medical care to this group of patients in the Russian Federation are highlighted, including in the framework of the programs “14 high-cost nosologies” and “17 nosologies” (17 life-threatening chronic progressive rare (orphan) diseases). The difficulties associated with the operation of the existing system of medical care for orphan patients are highlighted, including data on assessing the lack of information on management and on the procedure for providing information about patients with rare nosologies to the appropriate structures in the medical environment. The work also analyzes regional Russian and foreign screening programs, a review of relevant diagnostic methods and the experience of their implementation and use. The authors also address issues related to biotechnological innovations in Russian and foreign medicine, emphasizing the relevance, effectiveness and, in some cases, the indispensability of gene therapy. In conclusion, the authors summarize the most significant issues and challenges facing orphan medicine in the Russian Federation, as well as make suggestions for their solution.