Using Humanization we can take advantage of the ancient biology between humans and other organisms to create stand-ins – patient avatars – for drug screening studies. In this blog, we will focus on models of inborn errors of metabolism (IEM), as these genetic conditions can lead to hypersensitivity to the metabolite. Since stressor condition hypersensitivity can be used to detect favorable drug effects, IEM model systems are ideal tools for phenotypic screens to find molecules that alleviate the metabolic stress occurring from the deficiency. We discuss the model organisms used in hypersensitivity screens, and why they are advantageous to drug discovery. Ultimately, showcasing this approach’s potential to be widely generalized to many genetic disorders.