The possibility that functional, three-dimensional tissues and organs may be derived from pluripotent cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), represents one of the grand challenges of stem cell research, but is also one of the fundamental goals of the emerging field of regenerative medicine. New research has shown that when ES cells are cultured under the appropriate conditions, they can be driven to self-organize into complex, three-dimensional tissue-like structures that closely resemble their physiological counterparts, a remarkable advance for the field.