OBJECTIVE： To provide references and suggestions for building and improving the R&D incentive policies for orphan drugs in China. METHODS： The R&D incentive policies for orphan drugs in USA and the EU were compared in aspects of its legislative history， incentive measures and effects. And suggestions for improving related policies in China were put forward. RESULTS & CONCLUSIONS： The R&D incentive policies for orphan drugs in USA and the EU respectively started from Orphan Drug Act in USA （1983） and Orphan Drug Management Specification in the EU （1999）， then formed relatively complete system by continuous improvement. The USA and the EU showed differences in its certification standard， procedure and specific incentives [R&D funding， tax deduction， fee reduction， additional incentives for micro and small and medium enterprises （SMEs）， market exclusivity and special approval procedure]， etc. In terms of fee reduction， for example， prescription application fee， production cost and drug confirmation fee were exempted in USA， while arrangement assist fee， initial and follow-up fee， checking fee before approval， initial listing type were reduced to a certain percentage in the EU. After developing incentive policies for orphan drugs， there is great increase in numbers of recognized qualifications and listing， SMEs have become new force in orphan drug R&D， R&D investment covers all types of diseases， orphan drug R&D are becoming the main direction of drug innovation and biotechnology development. China should determine the relevant legislation of R&D incentives for orphan drugs as soon as possible， set certification and improve specific measures of R&D incentives for orphan drugs from multiple aspects， while strengthen the cooperation with other countries in qualification and R&D incentives.