Neutrophils, a key component of the immune system, release extracellular traps (NETs) to combat microbial infections. NETs are composed of chromatin and granule proteins that bind and kill microorganisms. The study reveals a novel cell death program in neutrophils where the nuclei lose their shape, chromatin homogenizes, and the nuclear envelope and granule membranes disintegrate, allowing the mixing of NET components. This process is distinct from apoptosis and necrosis and depends on the generation of reactive oxygen species (ROS) by NADPH oxidase. Patients with chronic granulomatous disease, who lack functional NADPH oxidase, cannot activate this cell-death pathway or form NETs. This ROS-dependent death allows neutrophils to fulfill their antimicrobial function even beyond their lifespan. The findings highlight a previously unknown form of active cell death that enables neutrophils to combat microbes effectively.Neutrophils, a key component of the immune system, release extracellular traps (NETs) to combat microbial infections. NETs are composed of chromatin and granule proteins that bind and kill microorganisms. The study reveals a novel cell death program in neutrophils where the nuclei lose their shape, chromatin homogenizes, and the nuclear envelope and granule membranes disintegrate, allowing the mixing of NET components. This process is distinct from apoptosis and necrosis and depends on the generation of reactive oxygen species (ROS) by NADPH oxidase. Patients with chronic granulomatous disease, who lack functional NADPH oxidase, cannot activate this cell-death pathway or form NETs. This ROS-dependent death allows neutrophils to fulfill their antimicrobial function even beyond their lifespan. The findings highlight a previously unknown form of active cell death that enables neutrophils to combat microbes effectively.