Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the articular synovium, resulting in bony erosions, deformity, and, ultimately, joint destruction. With associated comorbid conditions, especially cardiovascular, it can result in significant morbidity as well as early mortality. Patients with RA report impairments in health-related quality of life (HRQOL) in comparison with age- and sex-matched populations without arthritis. These decreases in HRQOL are attributed to the pain, impairment in physical function, and fatigue associated with this disease. The introduction of new disease-modifying antirheumatic drugs has revolutionized the treatment of RA, particularly the biologic agents: etanercept, infliximab, adalimumab, abatacept, and rituximab. Importantly, administration of these agents has resulted in statistically significant and clinically meaningful improvements in physical function and HRQOL. Many clinical studies confirm that with these therapies, RA patients report improvements in HRQOL, reflected by improved physical function, less fatigue, and better emotional and mental function. Maintenance of physical function is no longer the only treatment goal for RA but also to improve, restore, and preserve HRQOL. Results from pivotal clinical trials are analyzed in this article and the relevance of the data derived from the clinical studies to day-to-day clinical practice are also discussed.