Conventional insulin therapies involve multiple daily subcutaneous injections. However, the resultant disposition of insulin and blood glucose differs considerably from that following the physiological secretion of pancreatic insulin. A variety of alternative routes/methods have been investigated to improve systemic insulin delivery. Peroral and nasal insulin administration have demonstrated good potential for the treatment of diabetes. Facilitated transdermal delivery has also enjoyed success in promoting the systemic delivery of insulin. In addition, pulmonary, buccal, and ocular insulin administration have been shown to decrease serum glucose concentrations. Other methods that have been investigated for their potential in systemic insulin delivery include rectal, vaginal, and uterine routes.