This review focuses on recent advances in molecular biology as they pertain to the insulin gene and diabetes mellitus. The structure of the human insulin gene is examined, and factors related to its normal functioning in the beta cells of the pancreas are explored. DNA polymorphisms near the insulin locus and their relationship with certain types of diabetes are considered, as are recently characterized human insulin gene mutations. Events in animal models for diabetes that reflect altered insulin gene expression are discussed and the potential application of gene therapy in human diabetes is examined. Recombinant DNA methodology holds great promise as a tool for providing better understanding of the causes of diabetes and potential curative treatment.