Rheumatic diseases encompass a heterogeneous group of autoimmune and autoinflammatory disorders affecting joints, muscles, and connective tissue, with juvenile idiopathic arthritis (JIA) being the most prevalent among children. The introduction of biological agents in the treatment of childhood rheumatic diseases has significantly improved outcomes and quality of life. However, there is limited data on the use of biological agents in Jordanian children with these conditions. This study aims to evaluate the clinical indications for initiating biological agents and investigate the safety profile of biological therapy in Jordanian children. This retrospective study was conducted at Queen Rania Children's Hospital, including children (under 14 years of age) diagnosed with rheumatic diseases between January 2019 and December 2023. Data collected and reviewed included demographic characteristics, diagnosis, concomitant use of disease-modifying conventional synthetic antirheumatic drugs (csDMARD), indications for starting biological agents, age at initiation of therapy, and reported side effects during treatment. A total of 177 patients (57.6% females) with various rheumatic disorders were treated with biological therapy. The mean age at diagnosis was 7 years (range: 1-7 years), while the mean age at therapy initiation was 8.6 years (range: 4.2-14 years). JIA was the most common diagnosis in 110 patients (62%), followed by non-infectious uveitis in 18 patients (10.1%) and autoinflammatory disorders in 17 patients (9.6%). Concomitant therapy with DMARDs and corticosteroids was employed in 92.6% of cases (164 patients). A total of 290 biological treatments were administered, including infliximab (93
32%), etanercept (71
24.4%), adalimumab (48
16.5%), tocilizumab (41
14.1%), and anakinra (13
4.4%). In 66 patients (37.2%), the biological agent was switched, primarily due to inefficacy (56 patients, 84.7%) or adverse events (10 patients, 15.3%). A total of 64 adverse events (36.1%) were reported, the most common being infections (29
45.3%), local reactions (11
17.1%), and infusion-related reactions (10
15.6%). This retrospective study highlights the importance of evaluating the efficacy and safety of biological agents in treating childhood rheumatic diseases. The findings can help optimize treatment strategies and improve patient outcomes.