Birth defects among infants of diabetic mothers convey a major financial and sociologic burden to society notwithstanding the psychologic impact to the patients and families. Epidemiologic, clinical, and experimental studies indicate that these malformations occur in early pregnancy, are influenced by the abnormal maternal metabolic milieu, and seem to result from a combination of more than one factor. Clinical and experimental studies, however, have demonstrated that optimal metabolic control achieved in the periconceptual period and maintained throughout the first trimester of pregnancy results in a significant reduction in the malformation rate among offspring of diabetic mothers. In this light, diabetic women contemplating pregnancy should be encouraged to delay conception until satisfactory metabolic control is achieved so that embryogenesis may occur in an optimal metabolic milieu. The experimental use of arachidonic acid in the prevention of diabetes-related embryopathy is a new and potentially valuable tool. It extends the spectrum of available methods for prevention and deserves further study as a potential agent for pharmacologic prophylaxis.