Neutrophil extracellular traps (NETs) are formed by neutrophils, a type of white blood cell, as a last resort to control microbial infections. NETs consist of processed chromatin bound to granular and cytoplasmic proteins, and their release is a unique form of cell death called "NETosis." This review discusses the mechanisms of NET formation, their antimicrobial activities, and their roles in infections, autoimmunity, and coagulation. NETs are composed of smooth filaments with a diameter of ~17 nm, made of stacked nucleosomes, and studded with globular domains containing granular proteins. NETosis involves the loss of intracellular membranes before the plasma membrane is compromised, leading to the release of chromatin and granular components. The antimicrobial activities of NETs depend on their structure, which provides a high local concentration of antimicrobials. NETs can inactivate microbial proteins, kill or inhibit microbes, and have antiviral properties. However, excessive or improper NET formation can lead to pathologies such as cystic fibrosis, preeclampsia, coagulation disorders, periodontitis, and autoimmune diseases like systemic lupus erythematosus. The review also explores the evolutionary significance of NETs, suggesting that chromatin evolved with two functions: organizing DNA and defending against pathogens.Neutrophil extracellular traps (NETs) are formed by neutrophils, a type of white blood cell, as a last resort to control microbial infections. NETs consist of processed chromatin bound to granular and cytoplasmic proteins, and their release is a unique form of cell death called "NETosis." This review discusses the mechanisms of NET formation, their antimicrobial activities, and their roles in infections, autoimmunity, and coagulation. NETs are composed of smooth filaments with a diameter of ~17 nm, made of stacked nucleosomes, and studded with globular domains containing granular proteins. NETosis involves the loss of intracellular membranes before the plasma membrane is compromised, leading to the release of chromatin and granular components. The antimicrobial activities of NETs depend on their structure, which provides a high local concentration of antimicrobials. NETs can inactivate microbial proteins, kill or inhibit microbes, and have antiviral properties. However, excessive or improper NET formation can lead to pathologies such as cystic fibrosis, preeclampsia, coagulation disorders, periodontitis, and autoimmune diseases like systemic lupus erythematosus. The review also explores the evolutionary significance of NETs, suggesting that chromatin evolved with two functions: organizing DNA and defending against pathogens.