The management of patients with rheumatoid arthritis (RA) has changed dramatically in recent years, largely because of the unrivaled efficacy of biologic agents in ameliorating clinical disease activity and in preventing joint damage; however, the use of biologic agents is associated with medical risks and socioeconomic costs. Guidance is, therefore, needed to identify those patients who might benefit most from this intensive treatment approach--and to identify those individuals who can be spared the potential adverse effects of such treatment without risking disease progression. As reviewed here, a variety of serological, clinical, immunological, radiological, and genetic markers have been proposed to predict clinical outcome in RA. These markers can all be determined without difficulty; however, with the notable exception of the genetic markers and erosions, these parameters are for the most part indicative of inflammatory disease activity and, therefore, subject to variation. As tight control of disease activity dissociates the prognostic markers from the clinical course, these predictive parameters should be assessed at baseline for every patient and used to guide individualized treatment strategies.