01412nas a2200205   4500000000100000000000100001008004100002260001500043653002200058653001900080100001700099700001900116700003000135700001700165245009400182856005500276300000900331520085200340022001401192       2025                            d  c2025-11-1210aBiological models10aDrug screening1 aDaisong Wang1 aRemi Villenave1 aNadine Stokar-Regenscheit1 aHans Clevers00aHuman organoids as 3D in vitro platforms for drug discovery: opportunities and challenges  uhttps://www.nature.com/articles/s41573-025-01317-y  a1-233 aOrganoids are 3D structures derived from stem cells that recapitulate key architectural and functional aspects of the corresponding tissue. Compared with conventional 2D cell lines, human organoids provide experimental models that more closely reflect human physiology. Their ability to capture the complexity and heterogeneity of human tissues enables the study of disease mechanisms, drug efficacy and toxicity. When generated from patient material, organoids also allow the assessment of individual drug responses. In this Review, we explore the utility of organoids in drug discovery. We outline current methodologies for generating and maintaining organoids, examine their applications in disease modelling, drug screening and safety evaluation, and consider regulatory aspects and the challenges for their broader adoption in drug discovery.  a1474-1784