Rheumatoid arthritis (RA) affects an estimated 1.3 million Americans and is a complex inflammatory disease associated with synovitis and joint destruction. The development of biologic disease-modifying anti-rheumatic drugs (DMARDs) that target specific mediators of inflammation has led to several highly successful therapies for the treatment of RA. The imperfect efficacy of biologic DMARDs has resulted in the absence of clear guidelines on how biologic DMARDs should be used in the clinic to optimize treatment of RA patients. This makes it imperative that better data be available to physicians and RA patients about the comparative effectiveness of different biologic DMARDs. Prior to 2008, there were no randomized trials comparing biologic DMARDs for the treatment of RA. Since then, there have been published studies that directly compared biologic DMARDs for the treatment of RA, and several studies that estimated the relative efficacy of different biologic DMARDs by comparing published results of studies that included treatment of RA patients with biologic DMARDs who had previously experienced an inadequate response to methotrexate or tumor necrosis factor (TNF) antagonists. There are two recent studies that directly compared biologic DMARDs with optimal combinations of oral DMARDs and these are important because there are significant differences in costs and side effects between oral and biologic DMARDs. Among the studies that directly compared biologic DMARDs, it has been reported that RA patients who fail a TNF antagonist have a higher response rate (based on disease activity score [DAS28] measurements) to treatment with rituximab as compared with another TNF antagonist. In addition, in the ATTEST trial, the investigators found that, for RA patients with an inadequate response to methotrexate, treatment with abatacept versus infliximab resulted in response rates that were roughly equal. There are also several head-to-head studies of biologic DMARDs that are currently enrolling or about to enroll RA subjects. Pharmaceutical companies have taken more interest in comparative effectiveness studies, in part due to the emphasis that has been placed on this type of research by the US federal government and associated organizations including the Patient-Centered Outcomes Research Institute (PCORI). Therefore, while there is currently a relative lack of comparative effectiveness research to inform clinical decisions about biologic DMARDs for RA patients, it appears likely that there will be wider availability of such data in the near future.