Diabetes is a leading health problem of the world and its prevalence continues to rise. With Type I diabetes, and in some patients with Type II, the lack of insulin can be counterbalanced by providing new beta (insulin-producing) cells. For Type I diabetes, treating the autoimmune attack remains a serious challenge. Several strategies to produce new beta cells have been proposed. These include differentiation from embryonic stem cells, proliferation of existing adult beta cells, derivation from putative adult progenitors/stem cells, and reprogramming of non-beta cells to beta cells. Each of these strategies has distinct merits and risks, and they are at different stages of understanding and development. In particular, the approach based on differentiation from embryonic stem cells has had strong support and in recent years has made notable progress. Nevertheless, significant hurdles remain to transform the current research into future therapies. To expedite this transformation, we believe particular emphasis should be placed on overcoming key knowledge gaps in beta-cell biology, developing strategies that produce patient-specific beta cells, and carefully addressing potential treatment-related complications or limitations.