That functional differentiation is dependent on 3D architecture has become accepted recently. Many papers over the last 50 years have shown that cells cultured in 2D are not representative of the in vivo situation. Structurally, 2D cultures do not provide the conditions for the organization and cellular relationships observed in vivo. Moreover, cell signaling networks are altered in 2D versus 3D, and this probably explains why drug screening outcomes many times do not reproduce the in vivo setting (Wang et al., 1998; Weaver et al., 2002). It is encouraging to see the recognition of the importance of 3D cultures to model signaling, differentiation, and drug development. Many of the studies use elegant images and sophisticated animations that are a delight to see and hear about and clearly show the similarity between organoids and the tissues and organs from which the cells were derived in vivo. We applaud the excitement and cheer the general enthusiasm that the work has deservedly generated. What is most exciting is that the combined effort is finally a critical mass and as a result has caught
