Cytokines are pleiotropic substances that are known to participate in inflammatory and immune responses as well as cell differentiation and proliferation. Interleukin-6 (IL-6) is a key cytokine with pro-inflammatory function. Wound healing is a complex cascade of physiologic events comprising inflammation, proliferation and remodeling, and proceeds with the integrated actions of different cells, cytokines, and the extracellular matrix. Aberrant wound healing results in keloid formation which causes disfigured appearance, discomfort, psychological stress, and patient frustration. In this review, the role of IL-6 signaling pathway in the pathogenesis of keloid is assessed and its potential as a therapeutic target is addressed. The existing data suggest that IL-6 mediated inflammation is a key player and may be considered as a common causative factor for development of keloid. Furthermore, in a recent comprehensive study, we confirmed the functional role of IL-6 signaling in keloid pathogenesis. Accordingly, inhibitory strategies of IL-6 signaling pathway by targeting the IL-6 receptors, its downstream effecters, or other molecules influencing this pathway appear to have considerable potential as new therapeutic or preventive challenges for keloid. Hopefully, several IL-6 blocking agents including a humanized antibody to IL-6 receptor have been developed and successfully used in clinical trials of inflammatory diseases. It is likely that these agents may prove worthy in the treatment or prevention of keloid as well. Future in-depth exploration of such challenges will shed light on their efficacy and safety for clinical application in keloid.