Many of the embryonic and fetal abnormalities that occur in pregnancies complicated by maternal diabetes are the result of development in a metabolically abnormal environment. Diabetic embryopathy (birth defects and spontaneous abortions) results from maternal metabolic abnormalities during the first 6-7 weeks of gestation. The embryopathy appears to be multifactorial in origin, and the resulting defects remain important causes of morbidity and mortality in diabetic pregnancies. Diabetic fetopathy (predominantly macrosomia and neonatal hypoglycemia) results from fetal overnutrition and hyperinsulinemia during the second and third trimesters. Fetopathy may cause significant morbidity not only in the perinatal period, but also in later life as overweight infants grow up to be overweight children and young adults. Careful regulation of maternal metabolism from the preconceptional period onward can reduce greatly or even eliminate the excess risks that have been incurred by infants of diabetic mothers in the past. Successful management of maternal diabetes requires knowledge of the alterations in intermediary metabolism that normally occur during pregnancy, as discussed in this chapter.