Progress is being made in the development and application of methods to replace, reduce and refine the use of non-human primates (NHPs) in biomedical research and testing of products and devices. However, there remain considerable cultural and practical barriers to widespread uptake of available 3Rs techniques and to further advancement of the 3Rs in NHP research, over and above scientific obstacles. While most of these barriers apply also to the use of other vertebrate species, there is arguably a greater imperative to overcome them in the case of the NHPs, given their high sentience and the degree of societal concern about their use. To do so will require greater awareness among researchers of the availability and scientific benefits of 3Rs approaches; increased funding for the development of new research models and tools, infrastructure and training; more robust scientific and ethical review of research proposals involving NHPs; better retrospective evaluation of the benefits accrued from NHP research; and improved knowledge transfer. Change is not made without inconvenience, but fully applying the 3Rs to research involving NHPs can improve the quality of science, its translation, business efficiency and public support.