Carbohydrate-deficient glycoprotein syndrome consists of a group of disorders with multisystemic involvement and prominent neurologic symptoms. The full clinical spectrum continues to evolve, with four types currently recognized; type I is by far the most common. The clinical presentation of CDGS appears more severe in infants than in adults. Diagnosis is based on the clinical findings of characteristic fat distribution, neurologic impairment, and developmental delay, combined with the biochemical finding of cathodally migrating serum glycoproteins, transferrin in particular, on isoelectric focusing. Scientific evidence supports the hypothesis that abnormal synthesis of N-linked oligosaccharides is the basic metabolic defect in CDGS. The complex, multistep nature of the N-linked oligosaccharide pathway and the clinical heterogeneity of CDGS suggest that several different defects in the pathway can result in this disorder. Two specific enzyme defects have been reported: phosphomannomutase deficiency in some type I patients and N-acetylglucosamine transferase II deficiency in type II patients. Investigations continue into other metabolic bases of CDGS. The discovery of some of the enzyme defects paves the way for cloning, mutational analysis, and eventually prenatal diagnosis in appropriate families. No known treatment exists for CDGS; pallintive care and support is the most that can be offered. Family support systems are blossoming both in the United States and abroad, giving families the ability to communicate with each other and with workers in the field. As more cases are diagnosed and scientific research continues, advances in clinical definition, supportive care, nutrition, and prenatal diagnosis of CDGS are inevitable.