We highlight the disposition of various cell types to self-organize into complex organ-like structures without necessarily the support of any stromal cells, provided they are placed into permissive 3D culture conditions. The goal of generating organoids reproducibly and efficiently has been hampered by poor understanding of the exact nature of the intrinsic cell properties at the origin of organoid generation, and of the signaling pathways governing their differen- tiation. Using microtechnologies like microfluidics to engineer organoids would create opportunities for single-cell genomics and high-throughput functional genomics to exhaustively characterize cell intrinsic properties. A more complete understanding of the development of organoids would enhance their relevance as models to study organ morphology, function, and disease and would open new avenues in drug development and regener- ative medicine.