This review article by Tae Sung Kim and Niki M. Moutsopoulos explores the role of neutrophils and neutrophil extracellular traps (NETs) in oral health and disease, particularly periodontitis. Neutrophils are crucial in maintaining mucosal integrity and performing antimicrobial defense, but dysregulated neutrophil responses, including excessive NET release, can lead to various inflammatory and autoimmune diseases. The authors provide an overview of neutrophil functions, including NET formation, and discuss the mechanisms of NET activation and function in the context of periodontitis. They highlight the importance of neutrophils in controlling bacterial biofilms and preventing infection in the oral cavity. Genetic defects in neutrophil development and trafficking, such as Chediak-Higashi syndrome, Papillon-Léfèvre syndrome, and congenital neutropenia, are linked to severe forms of periodontitis. The article also reviews the presence and significance of NETs in periodontitis lesions, their antimicrobial properties, and their role in tissue destruction. Additionally, it discusses the broader implications of NETs in various inflammatory conditions, including autoimmune diseases, sepsis, atherosclerosis, and COVID-19. The authors conclude by emphasizing the need for further research to understand the complex roles of NETs in oral mucosal homeostasis and disease.This review article by Tae Sung Kim and Niki M. Moutsopoulos explores the role of neutrophils and neutrophil extracellular traps (NETs) in oral health and disease, particularly periodontitis. Neutrophils are crucial in maintaining mucosal integrity and performing antimicrobial defense, but dysregulated neutrophil responses, including excessive NET release, can lead to various inflammatory and autoimmune diseases. The authors provide an overview of neutrophil functions, including NET formation, and discuss the mechanisms of NET activation and function in the context of periodontitis. They highlight the importance of neutrophils in controlling bacterial biofilms and preventing infection in the oral cavity. Genetic defects in neutrophil development and trafficking, such as Chediak-Higashi syndrome, Papillon-Léfèvre syndrome, and congenital neutropenia, are linked to severe forms of periodontitis. The article also reviews the presence and significance of NETs in periodontitis lesions, their antimicrobial properties, and their role in tissue destruction. Additionally, it discusses the broader implications of NETs in various inflammatory conditions, including autoimmune diseases, sepsis, atherosclerosis, and COVID-19. The authors conclude by emphasizing the need for further research to understand the complex roles of NETs in oral mucosal homeostasis and disease.