Our understanding of the basic biology of diabetes has been guided by observations made using animal models, particularly rodents. However, humans are not mice, and outcomes predicted by murine studies are not always representative of actual outcomes in the clinic. In particular, investigators studying diabetes have relied heavily on mouse and rat models of autoimmune type 1-like diabetes, and experimental results using these models have not been representative of many of the clinical trials in type 1 diabetes. In this article, we describe the availability of new models of humanized mice for the study of three areas of diabetes. These include the use of humanized mice for the study of (1) human islet stem and progenitor cells, (2) human islet allograft rejection, and (3) human immunity and autoimmunity. These humanized mouse models provide an important preclinical bridge between in vitro studies and rodent models and the translation of discoveries in these model systems to the clinic.