OBJECTIVE: The disease burden in rheumatoid arthritis (RA) extends beyond the joint. This article evaluates the physical and psychosocial extra-articular burden of treated RA and relationships among diverse disease manifestations. METHODS: MEDLINE searches identified papers published in English from January 2003 to December 2012 that evaluated systemic complications and psychosocial aspects associated with RA. Preference was given to studies with randomized cohorts and large (>100) sample sizes. Of 378 articles identified in the initial search, 118 were selected for inclusion. RESULTS: RA is associated with multiple comorbidities and psychosocial impairments, including cardiovascular disease, osteoporosis, interstitial lung disease, infection, malignancies, fatigue, depression, cognitive dysfunction, reduced work performance, work disability, and decreased health-related quality of life. The etiology of the extra-articular burden may reflect the systemic inflammation and immune system alteration associated with RA, metabolic imbalances and side effects related to treatment, or the influence of comorbidities. Strategies that may help to reduce the extra-articular disease burden include personalized medicine and the potential introduction of treatments with new mechanisms of action. CONCLUSION: Despite improvements in treating joint disease, the extra-articular burden in RA remains substantial, encompassing multiple comorbidities and psychosocial impairments.