Effective management of rheumatoid arthritis (RA) is based on early treatment with pharmacological agents that are appropriate for the degree of disease activity and the presence or absence of indicators of poor prognosis. The 2012 American College of Rheumatology (ACR) treatment recommendations provide clear guidance for pharmacologic management of patients with RA. Although the optimal use of biologic and non-biologic disease-modifying drugs has transformed the treatment of RA to the extent that remission is a reasonable expectation, choice of a particular agent for use in a specific clinical situation remains unclear. Recently, Cochrane reviews as well as a Comparative Effectiveness Review by the Agency for Healthcare Research and Quality have examined the safety and efficacy of these drugs, with a particular emphasis on biologics. The conclusions of these reviews will be examined in the context of the ACR treatment recommendations.