This study delves into the perspectives of patients with rheumatic and musculoskeletal diseases (RMDs) on the symptomatic side effects of new prescription drugs. Through focus groups and interviews involving 34 participants with inflammatory arthritis across three continents, the research uncovers patients’ priorities regarding side effects. Key findings include the significant impact of side effects on various aspects of life (daily, family, work, and social life), the psychological and physical ramifications (including limitations to physical function, emotional dysregulation, and overall mental state), and the time, energy, and financial burdens associated with managing these side effects. Patients emphasized the importance of understanding the severity, frequency, and duration of side effects, as well as a comprehensive evaluation of the benefit-harm balance, which considers the cumulative burden of multiple side effects and their persistence over time. This study highlights the critical need for developing patient-reported measures that accurately reflect the impact of side effects and the benefit-harm balance in RMD treatments, offering a new perspective on patient-centered outcome assessment in clinical trials.