The 2021 American College of Rheumatology (ACR) Guideline for the Treatment of Rheumatoid Arthritis provides updated recommendations for the pharmacologic management of rheumatoid arthritis (RA). The guideline addresses the use of disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs (csDMARDs), biologic DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), as well as the use of glucocorticoids and DMARDs in high-risk populations. The recommendations are based on a systematic review of the literature and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A voting panel of clinicians and patients reached consensus on the direction and strength of recommendations. The guideline includes 44 recommendations, with 7 strong and 37 conditional. Strong recommendations are those where the panel is highly confident that the recommended option is beneficial and safe for most patients. Conditional recommendations are those where the panel is less confident about the benefits outweighing the risks. The recommendations are not prescriptive and emphasize shared decision-making based on patient values, goals, and preferences. Key recommendations include the strong preference for methotrexate over hydroxychloroquine or sulfasalazine for DMARD-naive patients with moderate-to-high disease activity. Methotrexate is also strongly recommended over bDMARD or tsDMARD monotherapy for such patients. Methotrexate monotherapy is conditionally recommended over combination therapy with other csDMARDs, and over methotrexate plus a TNF inhibitor. The guideline also addresses the use of glucocorticoids, recommending against long-term use due to significant toxicity. The guideline provides recommendations for specific patient populations, including those with subcutaneous nodules, pulmonary disease, heart failure, lymphoproliferative disorders, hepatitis B infection, nonalcoholic fatty liver disease (NAFLD), and nontuberculous mycobacterial (NTM) lung disease. For patients with NTM lung disease, abatacept is conditionally recommended over other bDMARDs and tsDMARDs. The guideline emphasizes the importance of shared decision-making and acknowledges the limitations of the evidence, particularly in areas where high-certainty evidence is lacking. The recommendations are intended to support clinician and patient decision-making and are subject to periodic revision as new evidence emerges. The ACR does not endorse any commercial products or services and encourages the use of the guidelines as a tool to guide clinical practice.The 2021 American College of Rheumatology (ACR) Guideline for the Treatment of Rheumatoid Arthritis provides updated recommendations for the pharmacologic management of rheumatoid arthritis (RA). The guideline addresses the use of disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs (csDMARDs), biologic DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), as well as the use of glucocorticoids and DMARDs in high-risk populations. The recommendations are based on a systematic review of the literature and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A voting panel of clinicians and patients reached consensus on the direction and strength of recommendations. The guideline includes 44 recommendations, with 7 strong and 37 conditional. Strong recommendations are those where the panel is highly confident that the recommended option is beneficial and safe for most patients. Conditional recommendations are those where the panel is less confident about the benefits outweighing the risks. The recommendations are not prescriptive and emphasize shared decision-making based on patient values, goals, and preferences. Key recommendations include the strong preference for methotrexate over hydroxychloroquine or sulfasalazine for DMARD-naive patients with moderate-to-high disease activity. Methotrexate is also strongly recommended over bDMARD or tsDMARD monotherapy for such patients. Methotrexate monotherapy is conditionally recommended over combination therapy with other csDMARDs, and over methotrexate plus a TNF inhibitor. The guideline also addresses the use of glucocorticoids, recommending against long-term use due to significant toxicity. The guideline provides recommendations for specific patient populations, including those with subcutaneous nodules, pulmonary disease, heart failure, lymphoproliferative disorders, hepatitis B infection, nonalcoholic fatty liver disease (NAFLD), and nontuberculous mycobacterial (NTM) lung disease. For patients with NTM lung disease, abatacept is conditionally recommended over other bDMARDs and tsDMARDs. The guideline emphasizes the importance of shared decision-making and acknowledges the limitations of the evidence, particularly in areas where high-certainty evidence is lacking. The recommendations are intended to support clinician and patient decision-making and are subject to periodic revision as new evidence emerges. The ACR does not endorse any commercial products or services and encourages the use of the guidelines as a tool to guide clinical practice.