A variety of tight junction (TJ) proteins including occludin, various claudins, junctional adhesion molecules, tricellulin and zonula occludens-proteins have been identified in complex localization patterns in mammalian epidermis. TJ structures were identified in the stratum granulosum and, in limited occurrence, in the stratum corneum. The expression and/or localization of TJ proteins and structures is frequently altered in skin diseases including skin tumors. Our understanding of the function(s) of TJ and TJ proteins in the skin has rapidly increased over the last decade. It was shown that TJ form a paracellular barrier in the stratum granulosum and are essential for skin barrier function. In addition, several lines of evidence hint for roles of TJ proteins in compartmentalization of the stratum corneum, polarization of the cells in the stratum granulosum, differentiation of the epidermis and cytokine production of keratinocytes. However, underlying mechanisms remain mainly unexplained. This lecture will give an overview of our current knowledge as well as nescience of functions of TJ proteins in the epidermis.