Medicine provision for patients with orphan diseases is the leading cost item for the healthcare system of each country in various regions of the world. Over the past decade, significant progress has been made in the provision of patients with orphan diseases in the Russian Federation. At the same time, a number of problems that limit the availability of necessary therapy remain at the federal and regional levels. In this article, we discuss the features of the organization of medicine provision for patients through various sources of financing. The availability of orphan medicines within the budget of the compulsory medical insurance fund and the high-tech medical care program is analyzed. Special attention is paid to the specifics of medicines provision regulation at the level of the subjects of the Russian Federation; recommendations are formulated for introducing a systematic approach to organizing this process. Taking into account the high priority of centralizing the procurement of orphan medicines, the authors developed a number of recommendations on optimizing the federal budget costs and ensuring the effective implementation of the task.