The expected explosive increase in the number of patients with diabetes mellitus will increase the stress on health care. Treatment is focused on preventing vascular complications associated with the disorder. In order to develop better treatment regimens, the field of research has made a great effort in understanding this disorder. This chapter summarizes the current views on the insulin signaling pathway with emphasis on intracellular signaling events associated with insulin resistance, which lead to the prothrombotic condition in the vasculature of patience with diabetes mellitus.