The push for more human-relevant, ethical, and efficient drug discovery methods is rapidly accelerating with the advent of human-derived in vitro models like organoids, organs-on-a-chip, human body-on-a-chip, and microphysiological systems (MPS). These technologies have the potential to revolutionize the drug discovery pipeline, offering more accurate insights into human biology and reducing the dependence on animal testing. However, their integration into mainstream drug development also presents unique challenges and opportunities.