Neutrophil extracellular traps (NETs) were first described over a decade ago as part of our innate immune system. Through the extracellular release of web-like structures composed of DNA and histones coated with antimicrobial peptides, the neutrophil was shown to entrap and disarm invading microorganisms. Recent data now propose a central role of NETs in a variety of non-infectious conditions - such as autoimmunity, thrombosis, and cancer - revealing that NETs may not only be beneficial, but also harmful if uncontrolled. Continued investigations into the clinical relevance of NETs will shed further light on the utility of biomarkers associated with NETs, and may open for new therapeutic options in several disease settings.