Some aspects of glucose homeostasis are regulated differently in males and females. This review discusses the most fundamental gender differences in glucose homeostasis and diabetes. These include the prevalence of impaired fasting glucose and impaired glucose tolerance, the prevalence and incidence of type 2 and type 1 diabetes, and the sex-specific effects of testosterone and estrogen deficiency and excess. These gender-specific differences in glucose homeostasis represent a source of factors that should be studied to develop gender-based therapeutic avenues for diabetes.