Defensins are small, multifunctional cationic peptides. They typically contain 
six conserved cysteines whose three intramolecular disulfides stabilize a 
largely β-sheet structure. This review of human α-defensins begins by describing 
their evolution, including their likely relationship to the Big Defensins of 
invertebrates, and their kinship to the β-defensin peptides of many if not all 
vertebrates, and the θ-defensins found in certain non-human primates. We provide 
a short history of the search for leukocyte-derived microbicidal molecules, 
emphasizing the roles played by luck (good), preconceived notions (mostly bad), 
and proper timing (essential). The antimicrobial, antiviral, antitoxic, and 
binding properties of human α-defensins are summarized. The structural features 
of α-defensins are described extensively and their functional contributions are 
assessed. The properties of HD6, an enigmatic Paneth cell α-defensin, are 
contrasted with those of the four myeloid α-defensins (HNP1-4) and of HD5, the 
other α-defensin of human Paneth cells. The review ends with a decalogue that 
may assist researchers or students interested in α-defensins and related aspects 
of neutrophil function.