In the second half of the 20th century it became obvious that a relentless increase in Type 2 diabetes mellitus (T2DM), affecting the economically affluent countries, is gradually afflicting also the developing world. This chapter shows the threat that the T2DM epidemic represents to mankind, with the astonishing recent discoveries on the role of obesity and of body fat in this metabolic disorder. Presently, the highest prevalence of T2DM is in Saudi Arabia. T2DM is very high in over 10% of adults in the USA, Switzerland and Austria. Prevalence is low in Norway, China and in Iceland. Predictions of epidemiologists for the first third of the 21st century claim up to 2.5 times increase in the prevalence of T2DM in the Middle East, Sub-Saharan Africa, India, rest of Asia and in the Latin America. In China the number of patients with T2DM will double in 2030. In the economically advanced countries the increase will be about 50% in 2030. Increasing urbanization, aging populations, obesity and falling levels of physical activity are all contributing to the rise of T2DM worldwide. The main cause of T2DM pandemic is growing prevalence of obesity in Europe and USA. In the North America and European Union countries obesity is considered to be responsible for up to 70-90% of T2DM in adult population. The precise mechanism by which obesity leads to insulin resistance and to T2DM is not completely known but it may be related to several biochemical factors such as abnormalities in free fatty acids, adipokines, leptin and other substances.