In recent years several seminal breakthroughs have revealed that tight junctions not only regulate barrier properties of simple epithelial cells but also play crucial functions in the regulation of the largest barrier of the organism, the stratifying epidermis of the skin. Here we will address the importance of tight junctions for the skin barrier function and discuss data from our studies and from others that indicate how cadherins, polarity, and other pathways may regulate these junctions in stratifying epithelia.