An optimal treatment approach to rheumatoid arthritis (RA) is guided by the American College of Rheumatology (ACR) 2012 recommendations. RA should be diagnosed early in the disease process and treatment should be commensurate with the degree of disease activity and the presence or absence of predictors of poor prognosis. The Agency for Healthcare Research and Quality (AHRQ) has recently provided a comparative review of medication for RA. The treatment of RA with conventional disease-modifying antirheumatic drugs and biologic agents, including tumor necrosis factor (TNF) inhibitors and non-TNF biologics (abatacept, rituximab, tocilizumab) will be discussed in the context of the ACR recommendations and the AHRQ review.