The development of stratified epithelia and their derivatives is a complex process requiring a multifaceted transcriptional program. p63, the p53-related transcription factor, is fundamental to this process. However, the underlying mechanisms by which p63 exerts its influence on stratified epithelial development and integrity remain elusive. Recent work from our laboratories has demonstrated that p63 mediates its effects on stratified epithelial function at least in part via its ability to regulate multiple aspects of epithelial cellular adhesion and survival. The identification of cell-cell and cell-matrix adhesion subprograms downstream of p63 provides an initial understanding of p63's role in epithelial development, integrity and homeostasis.