The importance of genetic factors in the aetiology of NIDDM has been underlined by study of family pedigrees and identical twin pairs. Although in some oisolated populations and a tiny minority of Western families inheritance follows an autosomal dominant pattern, a polygenic mode of transmission predominates in Europe and North America. No genetic markers have been identified despite intensive study of the HLA system and gene polymorphisms Enviromenmtal factors appear to play some role, but examiniation of the evidence for an aetiological effect of the commonly assumed factors, diet and obesity, suggest that they exert no direct effect. However, it is likely that these factors together with physical inactivity could modulate the speed of progression to symptomatic disesase. Both beta cell dysfunctions and tissue insulin insensitivity are important in producing the syndrome of NIDDM. Insulin insensitivity is present from very early ion the time course of the suyndrome, but it is clear that the disease cannot develop in the absence of beta cell dysfunction The recent discovery of islet associated amyloid is exciting as it represented a major step in tracing the pathogenesis of NIDDM backwards genetic and non-genetic aetiological influences.