OBJECTIVES: In Brazil, the studies produced by members of the Brazilian Network for Health Technology Assessment (REBRATS) have contributed in a significant way in the process of management and incorporation of technologies in the Brazilian Public Health system (SUS). However, there is still a lack of a Pharmaceutical Assistance and HTA Policy for rare diseases and the evidence for orphan drugs are limited and lower. The coverage for these drugs, is frequently done through judicial orders, political and social pressure, with no support of evidence-based medicine. The objectives is to evaluate the production of HTA studies for orphan drugs made by REBRATS members. METHODS: Query to the REBRATS database and the internal production of the HTA coordination, prioritizing 6 major diseases: Gaucher disease, Fabry disease, Mucopolysaccharidosis Type I (MPS I); Mucopolysaccharidosis Type II (MPS II); Mucopolysaccharidosis Type VI (MPS VI); Paroxysmal Nocturnal Haemoglobinuria (PNH). RESULTS: Five HTA studies were found, which are: a Rapid Response for Gaucher disease; a study on Health Technology Management for Fabry disease;  an Economic Evaluation for MPS I, II and VI; a Systematic Review for Mucopolysaccharidosis Type II; and one Rapid Review for PNH. For the evaluated Orphan Drugs, only the Eculizumabe for the treatment of PNH has no approved registration by the National Health Surveillance Agency (ANVISA). CONCLUSIONS: Considering its high cost, high judicial demand and limited availability of scientific evidence, orphan drugs represent a challenge for researchers and decision makers. Clinical benefit, disease severity, availability of therapeutic alternatives, ethical, political and social aspects should be considered. It is necessary to start a multidisciplinary reflection on the development of HTA models and policies regarding rare diseases and innovative treatments in the SUS, as well as fostering the primary researches in this field.