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Protein aggregation is the cause of several human diseases. Understanding the molecular mechanisms involved in protein aggregation requires knowledge of the kinetics and structures populated during the reaction. Arguably, the best structurally characterized misfolding reaction is that of α1-antitrypsin. α1-Antitrypsin misfolding leads to both liver disease and emphysema and affect approximately 1 in 2000 of the population. This review will focus on the mechanism of α1-antitrypsin misfolding and the development of potential therapeutic strategies. © 2008 IUBMB IUBMB Life, 61(1): 1–5, 2009 [ABSTRACT FROM AUTHOR]