This article reviews data concerning the applicability of anti-citrullinated peptide antibodies in the diagnosis, estimation of prognosis, and follow-up of patients with rheumatoid arthritis (RA). The production of anti-citrullinated peptide antibodies is closely associated with the presence of the HLA-DRB1 shared epitope, a known risk factor for development of RA, and the production may be influenced by environmental factors such as tobacco smoking. Patients who harbor this antibody from the early stage of their disease develop more severe erosive disease than patients with RA who lack the antibody. The anti-citrullinated peptide antibody level may be a reflection of disease activity, at least in the early phase of the disease. The antibody can sometimes be found several years before the onset of clinical symptoms of RA, which may represent an open window for preventive measures to be taken.