Diabetes mellitus is characterized by chronic high blood glucose levels resulted from deficiency and/or dysfunction of insulin-producing pancreatic β cells.Generation of large amounts of functional pancreatic β cells is critical for the study of pancreatic biology and treatment of diabetes.Recent advances in directed differentiation of pancreatic β-Iike cells from human pluripotent stem cells (hPSCs) can provide patient-specific and disease-relevant target cells.With the improved differentiation protocols,it is now possible to generate large amounts of functional human pancreatic β-like cells that can response to high level of glucose both in vitro and in vivo.Combined with precise genomic editing,biomedical engineering,high throughput profiling,bioinformatics,and high throughput genetic and chemical screening,these hPSC-derived pancreatic β-Iike cells will hold great potentials in disease modeling,drug discovery,and cell-based therapies.In this review,we summarize the recent progress in human pancreatic β-Iike cells derived from hPSCs and discuss their potential applications.