Non-invasive insulin delivery systems have potential to overcome the most pressing problem regarding effective treatment of diabetic patients: therapy compliance. To overcome this disadvantage, non-invasive routes such as oral, buccal, pulmonary, nasal and transdermal have been proposed. These new routes of insulin administration may help to suppress hypoglycemia episodes and aid to control weight gain and post-meal glucose. Despite all efforts the invasive route remains preferential, since studies on insulin administration by non-invasive routes conducted to date have not demonstrated clinical efficacy and safety, including some products introduced in the market. Therefore, the aim of this review is to make an update of the current state of administration of insulin by non-invasive routes as alternatives to the conventional invasive route.