The vascular endothelium has been identified as an important component in diabetes-associated complications, which include many cardiovascular disorders such as atherosclerosis, hypertension and peripheral neuropathy. Additionally, insulin’s actions on the endothelium are now seen as a major factor in the metabolic effects of the hormone by increasing access to insulin sensitive tissues. Endothelial function is impaired in diabetes, obesity, and the metabolic syndrome, which could reduce insulin access to the tissue, and thus reduce insulin sensitivity independently of direct effects at the muscle cell. As such, the endothelium is a valid target for treatment of both the impaired glucose metabolism in diabetes, as well as the vascular based complications of diabetes. Here we review the basics of the endothelium in insulin action, with a focus on the skeletal muscle as insulin’s major metabolic organ, and how this is affected by diabetes. We will focus on the most recent developments in the field, including current treatment possibilities.