A new generation of human model systems are coming to the forefront of drug development, including novel organoid, microphysiological, and in silico platforms. With the passage of the FDA Modernization Act 2.0 in 2022, these cutting-edge systems and are poised to gain increasing scientific, commercial, and regulatory acceptance in replacing data traditionally sought from animal models. But just how far can these systems go in displacing animals, and what commercial and regulatory challenges stand in their path? Join us as we convene a panel of experts in alternative human model systems to discuss their changing role in science and business.