In recent years diabetes has become one of the most common metabolic diseases in developed countries and it is closely related to supernutrition and obesity. Since untreated diabetes produces oxidative stress responsible for secondary complications of the disease, antioxidant supplements were considered as being favourable for the therapy of diabetes. However, the situation has changed recently, since large cross-sectional and interventional trials revealed a positive correlation between a high Se status and diabetes incidence in humans. Thus, currently available data on the role of Se in diabetes are inconsistent and an enigma appears to exist for the relation between selenium and diabetes. This review summarizes selected human and animal studies, pointing to beneficial and critical virtues of Se in diabetes. Moreover, the review discusses possible underlying mechanisms how Se may influence diabetes in both directions. From the current literature, the following information can be extracted: (1) In populations with a high Se status, with the single exception of pregnant women, Se supplements cannot be recommended for the prevention of diabetes; (2) Anti-diabetic effects of Se seem to be restricted to high and nearly toxic doses which cannot be used in humans; and (3) Future investigations should consider the stage of the disease.