For decades, investigators have made numerous attempts to generate human pancreatic β cell lines that could be used to advance β cell biology, facilitate drug discovery, and provide a pathway to β cell replacement therapy for the treatment of diabetes. In this issue of the JCI, Ravassard and colleagues report that this has finally been achieved successfully with a multistep process that led to the generation of cells, which they termed EndoC-βH1 cells, that secreted insulin in response to glucose challenge.