The early events leading to the development of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) remain unclear. In RA, formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules and that is dependent on the function of PADs. This presentation will highlight mechanisms by which citrullination of autoantigens and NETs contribute to the pathogenesis of a number of systemic autoimmunity and autoinflammatory syndromes, and potential therapeutic targets. Other posttranslational modifications will also be discussed.