When first published in 1959, Russell and Burch's book, The Principles of Humane Experimental Technique, 1 was considered ground-breaking. Defining, and advocating for, reduction, refinement and replacement, it held great promise for the movement away from animal use and toward the use of alternatives. However, what has been observed, in reality, since that time? After 65 years, it is apparent that these Three Rs principles did not elicit a rapid revolution; rather, we have witnessed a gradual and painstaking evolution in laboratory practice, where reduction and refinement have detracted from the more fundamental principle of replacement. In his thought-provoking review article, Bailey 2 addresses questions that have been raised regarding the success and impact of the Three Rs principles, asking "do they still have a role to play, both right now and in the future of biomedical research and testing? Or is it time for something different?". The article identifies failures within the traditional approach to the Three Rs that have hindered progress, but concludes more optimistically, that we may be at a "tipping point" with regard to the greater use of, and increased investment in, New Approach Methodologies (NAMs) to replace the use of animals.Whilst there is a justifiable argument to focus more on replacement than on reduction and refinement, most organisations devoted to alternatives currently seek to promote all Three Rs. The Korean Center for the Validation of Alternative Methods (KoCVAM) promotes the Three Rs and use of alternative methods in Korea. Kang and Oh describe some of the activities and accomplishments of KoCVAM, which include working with the International Cooperation on Alternative Test Methods (ICATM). 3 ICATM partners also include representatives from governmental organisations in the UK, EU, US, Japan, Canada, Brazil and China. Such international, collaborative effort is essential to coordinating a more unified approach to the development, validation and acceptance of alternatives. Greater co-operation between countries results in a more efficient and harmonised approach to animal replacement. Kang and Oh detail the contributions of KoCVAM to the development and validation of alternative test methods (including OECD test guidelines), and highlight some training courses delivered and videos created by the organisation to promote alternatives.Herein, Glaudo et al. describe a novel ex vivo model that is designed to simulate blinking and tear action in a method