Fibrinogen is a plasma clotting factor composed of three different polypeptide chains (alpha, beta and gamma). Under chronic inflammatory conditions, fibrinogen can be acted upon by the enzyme peptidylarginine deiminase 4 (PAD4), converting specific arginine residues to citrulline. Patients with rheumatoid arthritis (RA) produce antibodies that bind citrullinated human fibrinogen. The citrullinated fibrinogen and reactive antibodies form immune complexes in RA patients, and these immune complexes can stimulate macrophages. Recently, it has been discovered that immunizing certain strains of mice with citrullinated human fibrinogen can induce the production of anti-citrullinated human fibrinogen antibodies and the development of arthritis that shares many pathophysiological features of the human disease.