Objectives The aim of this work is to describe characteristics and to present marketing authorisation procedure for orphan medicines. In this thesis, availability and expenditure of these medicines will also be described. This work will analyse how approved orphan medicines contribute to the healthcare system and how the availability of these medicines differs across Europe. Material and Methods Drugs for the treatment of rare and severe illnesses, so-called orphan drugs, are intended to treat diseases so rare that sponsors are reluctant to develop them under usual marketing conditions. Rare diseases are life-threatening or chronically debilitating diseases, affecting not more than 5 to 10 000 people in the European Union. In 2000, the European Parliament adopted the Orphan Regulation which stipulated a number of incentives for the development of these medicines. The Regulation also defines the criteria for orphan designation of a particular medicinal product and defines incentives for the development and placing onto the market of designated orphan medicines. This has made a significant step in solving the problem of lack of medicines that have been tested and approved for the treatment of rare and severe diseases. In research of this topic, data were obtained searching literature by the topic of the research, subject of the research, authors and journals. Relevant articles were studied in analytical and critical manner and the most important results, discussions and conclusions were selected. Based on studied articles, own review of researched problems was performed. Results With the entry into force of the Orphan Regulation, the criteria for orphan designation of a particular medicine and the incentives for the development and marketing authorisation of medicines to which this status has been granted are defined. As a result of these incentives, there is an increase in the number of approved medicines for rare and severe illnesses. Once the European Commission issues approval for orphan medicine, a number of factors are needed to bring the medicine to the patient. Access to appropriate medicines for patients with rare diseases is a complex process involving the pharmaceutical industry, regulatory bodies as well as economic factors and political issues. Significant variability and inequality between the numbers of available medicines was observed in the European Union, while the countries of the Balkan Peninsula are still too small markets for many orphan drugs. Despite being European Union Member State for more than five years, Croatia is still below the European average for drug availability. Conclusion Providing information on rare diseases is a complex assignment because knowledge about their diagnosis, treatment, prevention and available services is partial and dispersed. The availability of drugs and the continued supply of affordable medicines of acceptable quality, safety and efficacy are essential to achieving universal health care. Lack of the right medicine at the right time can lead to failure in treatment, delayed treatment or even cause the use of desirable and more costly alternative medicines that increase the risk of medication errors and adverse events. Scientific research needs to be stimulated to increase existing knowledge and to continue to work on addressing deficiencies that reduce the availability of medicines to patients suffering from rare diseases.