The family of defensins are antimicrobial peptides found in many species. They have antibiotic, antifungal and antiviral activity and have a role in neutrophil function, chemotaxis, immunomodulation, cytotoxicity and NK cell activity. Defensins are small 2-6 KDa beta-sheet cationic peptides with intramolecular disulfide bonds. Mammalian defensins are divided into α-, β-, and θ-subtypes. Initially human alpha defensin peptides were identified in neuthrophils leading to the name human neuthrophil peptides (HNP). There are six α-defensins: human neutrophil peptides 1–4 (HNP-1–4) and human defensins 4 and 5 (HD-5, HD-6). HNP-1–3 have primary structures that only differ by a single residue at the N-terminus. HNP1-3 are primarily found in azurophilic granules and comprise up to 99% of the total defensin content of the neutrophils. HNP-1, HNP-2 and HNP-3 are encoded by two genes DEFA1 and DEFA3 localized to chromosome 8. DEFA1 and DEFA3 encode identical peptides except the conversion of the first amino acid from alanine in HNP-1 to aspartic acid in HNP-3; HNP-2 represent N-terminally truncated iso-form lacking the first amino acid. Activation of neutrophils leads to rapid release of HNP, which can be measured in plasma and other body fluids during infection and inflammation. The main function of defensins is disruption of membrane integrity and function leading to lysis of the microorganism. The involvement of defensins in phagocytosis, macrophage and neuthrophil activation, interaction with complement, immunomodulation through changes in cytokine production implicate a strong role in primary innate response against microbial invasion. The interaction of HNP-2 with the negatively charged lipids of the microbial membrane is initiated by the net charge of the peptide of +3 at pH7. The HNP-2 peptide has the following sequence: CYCRIPACIAGERRYGTCIYQGRLWAFCC and accessory disulfide bridges.