With the increasing incidence of diabetes mellitus (DM), it is imperative to develop novel treatments. Stem cells offer the potential for use as renewable sources of glucose-responsive, insulin-secreting cells. However, developing a consistent protocol to enrich beta-cells is not a trivial issue. The question whether embryonic, fetal, or adult stem cells offer particular advantages as the starting material remains to be resolved experimentally. While somatic cell nuclear transfer avoids many of the problems associated with heterologous transplantation, the problem of autoimmune destruction of the beta-cells in type 1 DM might still remain. This review summarizes the innovative treatment strategies for DM and considers the possible advantages and problems.