The earliest description of diabetes was documented in the writings of Hindu scholars as long as in 1500 BC. In 1921 the Canadian scientists Fredrick G. Banting, Charles H. Best, J. J. R. Macleod and James B. Collip discovered insulin, a peptide (small protein hormone) which lowers blood sugar. They extracted insulin from the islets of animal pancreases. A year later, in January 1922, bovine insulin was first given to humans by injection. The co-discoverers, in particular James Collip, continued their work to purify the insulin extract to make it safer and more effective. In 1936, protamine, a low-weight protein, was used to develop a suspension. In 1951 the amorphous 'lente' insulins- semilente, lente and ultralente were developed. After several years of laboratory work during the years 1963-1966 human insulin was chemically synthesized. In 1975, fully synthetic insulin was synthesized. Since 1996, different insulin analogues have been introduced worldwide. Insulin therapy is undergoing a paradigm shift now a days and at this hour we need to focus on the cardinal principles of initiating, optimizing, and intensifying the treatment for achieving adequate control.