α1-antitrypsin deficiency is a common recessive hereditary disorder associated with emphysema and, less frequently, liver cirrhosis. 1, 2 The α1-antitrypsin protein (also referred to as α1-proteinase inhibitor) is produced by the liver and protects the fragile lung alveoli from destruction by elastase released by neutrophils. Individuals with α1-antitrypsin serum concentrations of less than 11 μM are at high risk for the development of emphysema. The deficiency state is usually the result of homozygous inheritance of the Glu342Lys mutation of the α1-antitrypsin gene, the so-called Z variant. 1, 2 The risk is accelerated by 20 years by cigarette smoking, with smokers who are α1-antitrypsin deficient developing clinical manifestations of the disease in their late 30s to 40s. The serum deficiency of α1-antitrypsin is reflected in the lung, in which insufficient α1-antitrypsin is available to protect the fragile alveoli against destruction by neutrophil elastase. In 1981, on the basis of the understanding that the pathogenesis of the emphysema associated with α1-antitrypsin deficiency results from insufficient α1-antitrypsin to protect the lung parenchyma, my laboratory, then at the National Heart, Lung and Blood Institute, purified human α1-antitrypsin from pooled human plasma, and showed, in five individuals with α1-antitrypsin deficiency, that we could re-establish normal serum and lung concentrations in 4 weeks by weekly intravenous infusions of the purified protein. 3 In 1987, we did a larger trial administering purified α1-antitrypsin weekly to 21 patients with α1-antitrypsin deficiency over 6 months—again showing reestablishment of normal serum and lung α1-antitrypsin concentrations and function. 4 On the basis of these data, the US Food and Drug Administration approved the use of α1-antitrypsin augmentation treatment for patients with α1-antitrypsin deficiency and emphysema. Since 1987, more than 5000 patients with α1-antitrypsin deficiency worldwide have been given α1-antitrypsin augmentation treatment.