2019 marked the 60th anniversary of the publication of Russell and Burch’s influential book ‘The Principles of Humane Experimental Technique’ which developed the concept of the 3Rs; Replacement, Reduction, Refinement of the use of animals in research. The 3Rs subsequently became a bedrock of animal research ethics, as did the Harm Benefit Analysis a few decades later. In recent years, however, systematic reviews have revealed a lack of scientific rigour at every stage of animal research and its reporting, whilst other investigations have found a lack of clinical translation in many fields. This talk will explore how this new evidence challenges traditional ethical frameworks within animal research and calls into question their fitness for purpose.