3D cell-based assays, including organoids, spheroids, and advanced organ-on-chip systems, have grown in popularity in the scientific community. Compared to conventional 2D assays, 3D assays deliver more biological relevance, more closely mimic the tissue microenvironment, and offer extended culturing necessary to assess physiological drug effects. Still, their use in larger-scale drug screening programs is limited, despite these clear advantages. In this discussion, Dr. Terry Riss from Promega, Dr. Tim Spicer from Scripps Research, and Dr. Jan Lichtenberg from InSphero explored the latest state-of-the-art automated 3D cell-based assays and focused on progress and obstacles on the way to fully automated screening in 3D. During the event, our panelists address questions and topics, such as: - What are the advantages of moving to phenotypic screens in 3D? - How do you choose the right 3D modality (spheroid, organoid, other scaffold-based approaches) and supporting cells, for your research? - How do you select assays (biochemical vs. imaging vs. omics) from 3D models that automate well, and deliver consistent results? - Use cases for automated 3D cell-based assays in the drug R&D process, safety vs. discovery - What are the key hurdles, and how do we overcome them?