Few animal welfare issues are more controversial than scientific or educational animal use, partly because harms are sometimes deliberately inflicted on animals. Welfare impacts may occur during animal sourcing, transportation, housing, and both routine and invasive scientific procedures. Impacts depend on sentience levels, procedural invasiveness, environmental, social, or other factors, and mitigation strategies such as anaesthesia, analgesia (painkillers), and environmental enrichment. Animal welfare impacts are cumulative over time. Death is one of the most profound harms that may be inflicted. 192 million animals were used internationally in 2015 – the most recent recorded year – most of whom were killed. Around 2–19 million animals were used for educational purposes. However, systematic reviews have clearly demonstrated the very limited benefits of such research for human healthcare. This results both from limitations intrinsic to animal models, and from the ways in which they are used, with methodological flaws highly prevalent. Systematic reviews have also demonstrated that well-designed humane teaching methods normally produce learning outcomes as good or better than those achieved through harmful animal use. 3Rs alternatives include Replacement, Reduction, and Refinement of animal use. Compliance with 3Rs principles and best practice standards should become mandatory, during design, conduct, and reporting of animal experiments.