Alternative ways of engineering cells in vitro are being tested to realize their therapeutic potential. A fundamental enigma in modern biology concerns the molecular rules that govern how cells establish and maintain identity during development. These rules are the key to generating therapeutic cell types in vitro and the foundation of regenerative medicine. The isolation of embryonic stem cells (ESCs) has enabled scientists to recapitulate the process of embryonic development in a dish, by directing differentiation of ESCs with combinations of morphogens and growth factors to mimic embryonic development. These experiments assume that cell and tissue fates evolve along specific paths, and once established, remain fixed. But the advent of cellular reprogramming has fundamentally altered our view of the stability of cell identity, and dramatic demonstrations of the interconversions of mature cell types have introduced the provocative idea that cell identity can be engineered to play beneficial therapeutic roles.