The microbiota has emerged as an important regulator of the host immunity by the induction, functional modulation, or suppression of local and systemic immune responses. In return, the host immune system restricts translocation and fine tunes the composition and distribution of the microbiota to maintain a beneficial symbiosis. This paradigm applies to neutrophils, a critical component of the innate immunity, allowing their production and function to be influenced by microbial components and metabolites derived from the microbiota, and engaging them in the process of microbiota containment and regulation. The cross talk between neutrophils and the microbiota adjusts the magnitude of neutrophil-mediated inflammation on challenge while preventing neutrophil responses against commensals under steady state. Here, we review the major molecular and cellular mediators of the interactions between neutrophils and the microbiota and discuss their interplay and contribution in chronic inflammatory diseases and cancer.