Human embryonic stem cells (HESCs) are pluripotent cell lines derived from the inner cell mass (ICM) of embryos at the blastocyst stage. These cells possess self renewal capacity and differentiation potential to all three embryonic germ layers. These unique characters made HESCs an attractive research tool for studying early human developmental processes as well as a potential therapeutic tool for various human diseases. Here, we focus on HESCs as a cellular model for human disorders. The advantages of such models as well as the various methodologies to achieve HESCs carrying a genetic defect will be discussed.