Although animal welfare is practised as a modern interdisciplinary science, it originates in philosophical theories of ‘the good life’ and values from social movements. We provide a brief introduction to the predominant theories of animal welfare and relate these to the challenges of assessing the welfare of GM/GE animals that might have altered biological functions and behaviours. Many applied frameworks for animal welfare are hybrid views, which contain elements of the different theories. We outline some of these frameworks with particular emphasis on the 3Rs, Replacement, Reduction, and Refinement, due to its wide application in the scientific community. We address the emerging questions and dilemmas in the wake of the new editing tools and their potential impact on the welfare of laboratory animals, i.e., the ‘pros’ and ‘cons’ of tailoring animals to fit the experiments to which they will be subjected. Finally, we present three actual cases and relate these to the different approaches to animal welfare.