Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. To date, three MODY genes have been identified on chromosomes 20q [hepatocyte nuclear factor (HNF-4 alpha)/MODY1], 7p (glucokinase/MODY2) and 12q (HNF-1 alpha/MODY3). Mutations in glucokinase/MODY2 result in mild chronic hyperglycaemia due to reduced pancreatic beta-cell responsiveness to glucose as well as decreased net accumulation of hepatic glycogen and increased hepatic gluconeogenesis following meals. In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects and major hyperglycaemia associated with microvascular complications. The role of the three known MODY genes in susceptibility to the more common late-onset from of NIDDM remains uncertain. Genetic studies seem to exclude any function as major susceptibility genes, although they may play a minor role in a polygenic context or a major role in particular populations.