The discovery of insulin is one of the greatest milestones in medical history. This discovery revolutionized the use of peptides and proteins as therapeutic agents. For more than six decades, insulin from different animal sources was used, until the breakthrough in biotechnology made it possible to produce human insulin in sufficient amounts. The evolution of the biotechnological era gave rise to modified insulins to solve some of the bottlenecks in insulin therapy. Efforts are currently focused towards developing non-invasive insulin delivery systems, and there are Several competing technologies in different stages of development. The next few years will see several novel approaches to mimic the endogenous release and kinetics of insulin, and also many improved analogues designed to achieve better control and effective treatment of diabetes.