While there are numerous studies showing that neutrophil extracellular traps (NETs) contribute to autoimmune inflammation and cause bystander tissue injury, human individuals with genetic impairments in NET formation curiously often suffer from exacerbated autoimmune diseases and/or chronic inflammatory conditions. These findings are confirmed in some mouse models of systemic lupus erythematosus (SLE) and gouty arthritis, where an absence of neutrophils or impairment of NET formation leads to exacerbation of autoimmunity and chronic inflammation. Thus, aside from their role as archetypical pro-inflammatory cells, neutrophils in general, and NETs in particular, can also interrupt the self-amplifying loop of cell activation and cell recruitment that characterizes neutrophilic inflammation. Here, we review the current state-of-the-science regarding anti-inflammatory and immune-regulatory action of NETs. We give an overview about the mechanistic involvement of NET-associated neutrophil serine proteases and suggest how tailored induction of NET formation could be exploited for the treatment of chronic autoinflammatory disorders.