Recent studies have advanced our understanding that the regulation of immune responses is not only confined to immunocompetent cells. Upon stimulation, keratinocytes are capable of releasing various factors and expressing receptors that are significantly involved in immunoregulation. Dysregulation and the abnormal production of cytokines and other inflammatory mediators as well as their receptors can be observed in various skin diseases. An understanding of keratinocytes as important regulators of the skin immune system opens new opportunities for the treatment of various skin diseases.