The Animal Models and Alternatives Work Group was initiated in June 2022 with a focus on educating the scientific community and the public about the role of animal tests and New Alternative Methods (NAMS) in basic research and regulatory science. Animal research has proven valuable in understanding normal biology and disease processes, developing therapeutics, and evaluating new products for potential efficacy and adverse effects that could affect human health or other species. It is unethical to test agents such as novel drugs, devices, or biologics in humans without identifying potential toxicities. Many NAMS (e.g., in vitro assays such as microphysiological systems, computational approaches) are being explored with a focus on the 3Rs (replace, reduce, and refine animal tests). This is likely to be an iterative process, with progress occurring in stages and steps, rather than all at once. One of the most difficult steps in replacing animal testing would be in regulatory assessments because classical nonclinical tests assess >40 organs and tissues and the integration of effects on the structure and function of these to predict adverse effects in humans. This group will explore where animals play key roles in discovering new therapies, developing models of disease, nonclinical testing of drugs and other products, in implementing the 3Rs, and identifying data gaps in terms of toxicity and efficacy assessments. We also will investigate where NAMS can serve important roles and move us toward the 3Rs. Our mission is to educate, which will involve hosting webinars and publishing papers and educational materials on the use of animals and NAMS.