This article describes the use of tumor necrosis factor (TNF) inhibitors in children, reviews the pharmacology of these agents, and reviews and summarizes the current safety information available for etanercept, adalimumab, and infliximab. TNF inhibitors are being used for a variety of indications in children including Crohn's disease and juvenile idiopathic arthritis. However, the full safety profile of these agents is still not known. In adult patients, TNF inhibitors have demonstrated a variety of adverse effects including increased risk of infection, malignancy, demyelinating disorders, and reactivation of latent diseases. In children the rate of adverse effects is harder to elucidate due to the limited number of patients in clinical trials and limited case reports. However, based on the data available, TNF inhibitors have been implicated in increasing the rate of malignancy in children, especially the rate of lymphoma. In addition, similarly with adults the rate of infections is increased and the types of infections are more rare or opportunistic. One of the more common adverse effects continues to be infusion or injection-site reactions, although children tend to have a lower rate of infusion reactions with infliximab compared to adults. Based on the limited safety information and long-term effect data, TNF inhibitors should be reserved in children for patients with refractory disease and the risks need to be understood and assessed prior to initiation.