Diabetes mellitus affects approximately 5% of the general population with its prevalence varying between ethnic groups and geographic regions. The majority of cases are either type 1 or type 2 diabetes. Although these disorders share a common phenotype, fasting and postprandial hyperglycemia, their etiology is distinct. A growing body of evidence has demonstrated a link between mitochondrial functioning and type 2 diabetes. Certain mitochondrial DNA (mtDNA) mutations affect insulin secretion involving an attenuation of ADP/ATP levels leading to a re-setting of the glucose sensor in the pancreatic β-cell. Co-morbid conditions include impaired hearing, changes in pigmentation of the retina, gastrointestinal abnormalities, cardiomyopathy, and MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). © 2010 Elsevier B.V., All rights reserved.