Recent studies have shown that mutations in four transcription factors, hepatocyte nuclear factor-4 alpha (HNF-4 alpha), hepatocyte nuclear factor-1 alpha (HNF-1 alpha), hepatocyte nuclear factor-1 beta (HNF-1 beta), and insulin promoter factor-1 (IPF-1), are responsible for maturity onset diabetes of the young (MODY) which is characterised by an early age of onset and autosomal dominant inheritance. MODY is not an uncommon disorder and in fact could account for about 2 to 5% of all cases of type 2 diabetes. Moreover, mutations in HNF-1 beta, which functions as a homodimer or a heterodimer with HNF-1 alpha, have been identified in a few families with MODY and severe kidney disease. Mutations in the coding regions or in the promotors of these nuclear factors are responsible for severe insulin secretory defects and for major hyperglycaemia associated with microvascular complications. The role of transcription factors in the development of the more common late-onset type 2 diabetes is still under investigation. Some mutations in HNF-1 alpha were identified in subjects with atypical forms of insulin-dependent diabetes, and a mutation in HNF-4 alpha and several mutations in IPF-1 were found in type 2 diabetic families with typical late-onset NIDDM. Altogether, these data suggest that non-MODY monofactorial forms of late-onset NIDDM, due to islet transcription factor defects, exist.