Neutrophils are the foot soldiers of the immune system. They home in to the site of infection and kill pathogens by phagocytosis, degranulation, and the release of web-like structures called neutrophil extracellular traps (NETs) that trap and kill a variety of microbes. NETs have been shown to play a multitude of additional roles in immunity but have also been implicated in inflammatory and autoimmune disease. Here, we discuss the role of NETs in these various contexts with a particular emphasis on the molecular mechanisms that regulate NET release and clearance. We highlight the comprehensive concepts and explore the important open questions in the field.