Cytokines are soluble peptides and proteins that are predominantly produced and secreted by immune cells. In numerous animal experiments the endogenous increase or application of exogenous pro-inflammatory cytokines is associated with pain behavior. In turn, cytokine inhibitors reduce such pain behavior in inflammatory and neuropathic pain models. Several clinical studies point out that cytokines are also important in different human pain states. Several chronic pain syndromes are associated with systemic pro-inflammatory cytokine profiles. In some pain syndromes these pro-inflammatory profiles are accompanied by a lack of analgesic anti-inflammatory cytokines. Numerous case reports and open clinical studies, but also some controlled trials show successful analgesic treatment using cytokine inhibitors. The following review article summarizes the main data of animal experiments and clinical trials concerning the role of cytokines in pain and the potential importance of cytokine modulation in pain treatment.