The purpose of our article is to critically assess if TallyHo mice are a true mouse model for type 2 diabetes and Alzheimer's disease. Diabetes is a lifestyle condition that is characterized by elevated blood glucose due to either insufficient amount of insulin or the body's inability to use the produced insulin efficiently. Diabetes occurs in multiple forms, including type 1, type 2, type 3, neonatal, and gestational. Type 2 diabetes covers 95% of overall diabetes, found in individuals 65 years of age and above. Both modifiable and non-modifiable factors are involved in developing diabetes. In patients with diabetes, increased blood glucose levels are reported to induce multiple complications, such as heart disease, stroke, kidney failure, foot ulcers, and damage to the eyes. However, the molecular basis of diabetes is not completely understood. Further, there are no accurate animal model(s) that mimic both type 1 and type 2 diabetes of humans. Multiple polygenic models are being used, including the Goto-Kakizaki rat, the Otzhka Long-Evans Tokushima Fatty rat, the Nagoya Shibata Yasuda mouse, the New Zealand obese mouse, the Tsumura-Suzuki obese diabetes mouse, leptin deficient ob/ob and the leptin receptor deficient db/db mouse models. In 2001, Kim and colleagues described the TallyHo mice that represent many features of type 2 diabetes of humans. Since then, several groups studied TallyHo mice. Only the male mice develop hyperglycemia and the females exhibit features of obesity. Thus, this model can be used to study both diabetes and obesity. The purpose of this article is to discuss recent developments in TallyHo mice research including diabetes onset and progression.