In 1974 a seminal paper drew attention to the very high rates of type 2 diabetes in many native populations of the Americas, Greenland, Polynesia, Micronesia and Melanesia (West 1974). West suggested that diabetes was probably uncommon in these groups prior to 1940, and noted that rates were still very low in those least touched by market economies. The high rates of diabetes in these populations were initially most often ascribed to a genetically based susceptibility to the development of obesity and associated diseases on the adoption of a western way of life. This explanation is commonly known as the ‘thrifty genotype’ hypothesis. An alternative explanation is that the susceptibility of these populations lies solely in the rapid changes of lifestyle they have experienced. Thus, it has been suggested that those born into a relatively poor environment may, if they later encounter a more western environment, be vulnerable to the development of obesity-related diseases. This latter explanation is sometimes referred to as the ‘thrifty phenotype’ hypothesis, to highlight its contrast with the thrifty genotype hypothesis. In this chapter I describe the populations best known for their very high rates of type 2 diabetes and cardiovascular disease, and then go on to consider in detail the competing explanations offered for these high rates of disease. I focus particularly on the debate about the causation of type 2 diabetes.