In the absence of head-to-head trials, analysis of available data from randomized clinical trials allows for comparison of the efficacy of biologic agents for the treatment of rheumatoid arthritis. Methotrexate (MTX) inadequate responder trials provide data suggesting no major differences among any of the biologic agents, which is also confirmed in MTX naive population trials, when available, possibly a more reliable comparison group. The decision to pick one over the other should focus on safety, long-term survival of the drug and ease of use, which is for the most part influenced by patient preferences.