Cytokines are a large group of polypeptides and small proteins that are effector molecules for cells involved in immune and inflammatory responses. There are agonists and antagonists that interact with each other to maintain a dynamic equilibrium, and ensure eventual recovery of any perturbation, for example, by trauma or infection, of the network toward inflammation. The imbalance between pro- and anti-inflammatory cytokines and the T helper cell subtypes is considered important in the pathogenesis of autoimmune diseases, including juvenile idiopathic arthritis. The measurement of cytokines and chemotactic cytokines in body fluids and synovial tissue has provided insight into the type of immune and inflammatory reaction and the possible presence or absence of regulation. Differences between subtypes of juvenile idiopathic arthritis have been identified with these measurements. But cytokine measurements in serum are not useful for diagnostic purposes, because of the variability during 24 hours, the collection and assay methods, as well as the ease of degradation for most cytokines. The recent interest in the genetic polymorphisms of cytokine genes and their association with juvenile idiopathic arthritis has provided association with a number of cytokine alleles. Confirmation of linkage with disease is only available for tumor necrosis factor and interleukin-6 at present. These genetic variants may be the basis of genetic susceptibility to the persistent imbalance in the inflammatory and immune networks, and determine the phenotype and severity of disease.