Despite the importance of insulin signaling pathways in human disease, initial concerns that insect physiology and sugar metabolism differ enough from humans that flies would not model human disease hampered research in this area. However, during the past 10–15 years, evidence has accumulated that flies can indeed model various aspects of diabetes and related human disorders. This cluster of diseases impact insulin and insulin signaling pathways, fields which have been discussed in many excellent review articles in recent years. In this chapter, we restrict our focus to specific examples of diabetes-related disease models in Drosophila, discussing the advantages and limitations of these models in light of physiological similarities and differences between insects and mammals. We discuss features of metabolism and sugar regulation that are shared between flies and mammals, and specific Drosophila models for Type 1 and Type 2 diabetes, Metabolic syndrome, and related abnormalities including insulin resistance and heart disease. We conclude that fly models for diabetes and related disorders enhance our ability to identify genes and discern functional interactions that can be exploited for disease intervention.