Diabetes mellitus is the most common endocrine disease, consuming almost 15% of annual health care expenditures in the United States. The focus of this review is on type II (non-insulin-dependent) diabetes mellitus, which accounts for approximately 90% of diabetic patients. The current understanding of the pathogenesis of type II diabetes is multifaceted. Complex defects in both insulin action and insulin secretion produce the metabolic derangements responsible for the disease. The pathophysiology is the result of a combination of polygene defects and environmental factors. The search for the responsible gene or genes is described and several candidate genes are discussed. Diabetogenes are addressed in the context of type II diabetes representing a prototype for the identification of the genetic basis of common diseases.