In pancreatic beta-cells, mitochondria play a central role in coupling glucose metabolism to insulin exocytosis, thereby ensuring strict control of glucose-stimulated insulin secretion. Defects in mitochondrial function impair this metabolic coupling, and ultimately promote apoptosis and beta-cell death. Various factors have been identified that may contribute to mitochondrial dysfunction. For instance mutations of the mitochondrial genome associated with diabetes, oxidative stress and reactive oxygen species, sensitivity of mitochondria to lipotoxicity, or the adaptative dynamics of mitochondrial morphology. Better comprehension of the molecular mechanisms contributing to mitochondrial dysfunction will help drive the development of effective therapeutic approaches.