Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood. Many questions regarding the risk of infection associated with JIA and with the immunosuppressant therapeutic agents commonly used to treat JIA are currently unanswered. It appears likely that JIA itself increases the background rate of serious bacterial infections, irrespective of immunosuppressant use. The available evidence suggests that treatment with methotrexate or tumor necrosis factor inhibitors only modestly increases the risk of serious infections and may not increase the risk at all. Opportunistic infections are very uncommon among children with JIA, but they likely occur at an increased rate compared to children without JIA. Intra-articular glucocorticoid injections almost never result in infectious complications in the treatment of JIA when performed carefully. Additional controlled studies of the risks of infection among children with JIA are needed, particularly comparative studies of newer therapeutic agents.