Protein citrullination is a post-translational modification of arginine that controls a diverse array of cellular processes, including gene regulation, protein stability, and neutrophil extracellular trap (NET) formation. Histone citrullination promotes chromatin decondensation and NET formation, a pro-inflammatory form of cell death that is aberrantly increased in numerous immune disorders. This review will provide insights into NETosis and how this novel form of cell death contributes to inflammatory diseases, with a particular emphasis on its role in thrombosis. We will also discuss recent efforts to develop PAD-specific inhibitors.