For almost 30 years, the non-obese diabetic (NOD) mouse has served as the primary model for dissecting the genetic and pathogenic basis for T-lymphocyte-mediated autoimmune type 1 diabetes (T1D). However, while sharing many similarities, it is becoming increasingly appreciated that there are also some differences in the immunopathogenic basis of T1D development between humans and NOD mice. This review will focus on aspects of T1D development in NOD mice that are similar and different from that in humans.