Insulin-producing β cells are lost or insufficient in diabetic patients, presenting the medical challenge for new β cells. Currently, there are three strategies that offer promise. One involves the generation of β cells de novo by directing the differentiation of either embryonic stem cells or induced pluripotent cells to the β cell lineage. The second is based on the conversion of another terminally differentiated cell to β cells in a process called reprogramming. The third approach is to promote the replication of existing β cells either in vivo or in vitro. Significant progress is evident for each strategy, but it remains unclear which approach will ultimately prove successful.