Treatments for rheumatoid arthritis (RA) over the last few decades have transformed the future outlook of the disease. Although patients with clinically apparent RA have a number of therapeutic options, all are associated with the risk of adverse events (AEs). Such therapeutics, facilitated by the identification of novel biomarkers and environmental and genetic factors to predict RA, may allow early detection, prompt treatment, and prevention before the future development of clinically apparent disease. Before choosing such treatments to make informed decisions in this context, however, accurate quantification of benefits and harms of such treatments is vital for participants without symptoms. This review summarizes the AEs reported in trials in preclinical or very early RA, the frequency and risk of primary AEs of concern associated with disease-modifying antirheumatic drugs (conventional, biologic, and targeted), glucocorticoids, and analgesia in clinically apparent RA. Also summarized is the evidence to date to support the quantification of benefit and harms incorporating patient preferences.