Introduction: The introduction of biological therapies opened a new era of treatment of juvenile idiopathic arthritis. After 15 years of experience with the first biologics for treatment of pediatric rheumatic disease, long-term safety effects are of great interest. Areas covered: This review summarizes published knowledge about safety aspects from clinical trials as well as from biologic registries in juvenile idiopathic arthritis patients. Beside infusion and injection reactions, the occurrence and aggravation of infections, the occurrence of a second autoimnnune diseases, including uveitis, psoriasis, chronic inflammatory bowel disease, multiple sclerosis, diabetes mellitus, as well as cytopenias and the development of malignancies are major concerns regarding treatment with biologics. Expert opinion: The safety profiles of approved biologics, the TNF-alpha inhibitors etanercept and adalimumab, and the IL-6-inhibitor tocilizumab are highly acceptable. This conclusion is not easily expandable to the IL-1 inhibitor as well as the T-cell-activation-inhibitor abatacept due to lack of experience; however, both have showed an excellent safety profile so far. An increase in knowledge about risk profiles in national and international collaborations, with national as well as international registries, is necessary.