Replication of β cells is an important source of β-cell expansion in early childhood. The recent linkage of type 2 diabetes with several transcription factors involved in cell cycle regulation implies that growth of the β-cell mass in early childhood might be an important determinant of risk for type 2 diabetes. Under some circumstances, including obesity and pregnancy, the β-cell mass is adaptively increased in adult humans. The mechanisms by which this adaptive growth occurs and the relative contributions of β-cell replication or of mechanisms independent of β-cell replication are unknown. Also, although there is interest in the potential for β-cell regeneration as a therapeutic approach in both type 1 and 2 diabetes, little is yet known about the potential sources of new β cells in adult humans. In common with other cell types, replicating β cells have an increased vulnerability to apoptosis, which is likely to limit the therapeutic value of inducing β-cell replication in the proapoptotic environment of type 1 and 2 diabetes unless applied in conjunction with a strategy to suppress increased apoptosis.