Induced pluripotent stem cell (iPSC) technology has provided previously unanticipated possibilities to model human disease in the culture dish. Reprogramming somatic cells from patients into an embryonic stem cell–like state followed by differentiation into disease-relevant cell types can generate an unlimited source of human tissue carrying the genetic variations that caused or facilitated disease development . Yet, despite the excitement over this “disease-in-a-dish” approach, studying genetic disorders in patient-derived cells faces more challenges than studies using genetically well-defined model systems. Here we describe some of these limitations, and also present some solutions for ensuring that iPSC technology lives up to at least some of its promise.