Human pluripotent stem cells including embryonic stem cell (hESC) and induced pluripotent stem cell (hiPSC) are able to differentiate into various somatic cell types in the body. Successful gene targeting in hESC/hiPSC enables not only to correct human diseases-associated mutations prior to clinical transplantation but also genetic engineering of human genome for basic research. By using the genetically modified hESC/hiPSC, biologists and physicians have found a way to study the pathogenesis and mechanism of human diseases, screen for novel drugs, and develop relevant therapeutic strategies. The combination of stem cell biology and gene editing technology will open a new avenue to advance the understanding of human diseases and develop related therapies.