The 'life cycle' of established rheumatoid arthritis can be divided into four phases. The first is the period leading up to the onset of arthritis. The second is the period during which persistence or remission is determined. The third is the evolution into a specific form of inflammatory arthritis, and the fourth is the outcome/severity of that arthritis. In some patients, these four phases follow in rapid succession; however, in other patients, the time course is prolonged over several months or years. This chapter explores the hypothesis that these four phases are distinct in the majority of patients, and that different genetic and environmental factors influence the various phases. It investigates the suggestion that a defect in the hypothalamic-pituitary-adrenal axis may underlie the persistence of inflammatory arthritis. It suggests that the term 'early rheumatoid arthritis' is not appropriate and that patients either have established rheumatoid arthritis or an undifferentiated inflammatory arthritis.