Factors derived from adipose tissue are believed to play a central role in the development and progression of diabetes and its vascular complications. Insulin resistance and vascular function are directly affected these factors, i.e., by free fatty acids, inflammatory adipocytokines, thrombotic and antifibrinolytic factors and by adiponectin, and adipokine with insulin sensitizing and anti-inflammatory actions. Targeting these factors by antidiabetic agents should result in improved metabolism and in a reduction of vascular risk. We therefore analyzed antidiabetic treatment strategies with regard to improvements of adipose tissue derived risk factors. This shows that weight loss remains an extremely powerful tool to reduce all of these risk factors. Thiazolidinediones and rimonabant are most potent in improving numerous adipose derived risk factors but studies demonstrating reduced mortality are not yet available. Metformin has little effect on any of the adipose tissue derived factors but appears to reduce diabetes related mortality according to limited evidence. Sulfonylureas and insulin have rather limited effects on adipose tissue derived factors and are likely to exert beneficial effects mainly by improved glucose metabolism and its consequences.