The pathophysiology of alpha 1-antitrypsin (AAT) deficiency and the use of alpha 1-proteinase inhibitor therapy in the management of emphysema caused by AAT deficiency are described. AAT deficiency is the most common genetic cause of liver disease in children and emphysema in adults. However, not all patients with AAT deficiency develop hepatic or pulmonary involvement. Changes in the composition of the AAT molecule have been associated with AAT dysfunction in liver disease, whereas lung disease occurs when AAT concentrations are reduced. A definitive diagnosis can be made through serum AAT phenotype determination. Therapy for liver disease induced by AAT deficiency consists of supportive measures. Therapy for pulmonary disease due to AAT deficiency includes AAT augmentation therapy along with supportive measures. The available product, alpha 1-proteinase inhibitor, is derived from fractionated plasma and has similar biological activity to native serum AAT. Clinical trials have demonstrated a positive effect on serum and lung concentrations of AAT with few adverse events. Two recombinant forms of AAT have also been developed; however, few trials have been published evaluating their safety and efficacy in AAT-deficient patients. Many questions remain unanswered concerning AAT deficiency and replacement therapy. AAT augmentation therapy appears to reduce the progression of emphysema in some AAT-deficient patients.