Insulin therapy has now been with us for close to 100 years and widely used for type 1 and type 2 Diabetes Mellitus. Because hypoglycemia and weight gain remains unpredictable for the most part and limits insulin dosage, its use is limited in this respect. Human insulin, manufactured by the recombinant DNA technology, was introduced in the early 1980s. This technology allowed the manufacture of novel insulins and insulin analogues of human insulin. The use of insulin in type 1 diabetes remains essential. A problem for insulin therapy in type 2 diabetes is that it is used later in the course of the condition, and is often used where medical management is more difficult and critical. Particular safety issues that need to be addressed and would be discussed are the arterial wall proliferation hypothesis, CV safety, and growth factor promotion of malignancy. Compared with oral agents and independent of the level of glycaemia achieved, insulin does not appear to prevent or increase major adverse cardiovascular events. In addition, the type of insulin does not affect cardiovascular outcomes. Although insulin therapy remains essential in diabetes, the necessity and benefits of its use and the development of new insulins with less risk of hypoglycemia , would be able to balance a high degree of concern over any safety issue.