Resident pools of somatic stem cells in many organs are responsible for tissue maintenance and repair. The goal of regenerative medicine is to exploit these cells either by transplanting them from an exogenous source or by activating endogenous stem cells pharmacologically. For diseases caused by mutations in a single gene, the therapeutic goal is tissue replacement using stem cells engineered to correct the genetic defect. However, a number of technical hurdles must be overcome before therapies based on pluripotent human stem cells can enter the clinic.