The epidermis is composed of keratinocytes which undergo a highly reproducible terminal differentiation program resulting in the formation of a protective barrier, which is established during embryogenesis. Significant progress has recently been made in understanding the genetic pathways associated with the earliest event characteristic of epidermal morphogenesis, commitment to stratification. This process depends on the expression of p63, a transcription factor which is transcribed into isoforms that contain (TA) or lack (AN) a transactivation domain. In the absence of p63 expression, epithelia remain single-layered, while ectopic TAp63alpha expression in single-layered epithelia initiates stratification. Later events during epidermal morphogenesis require withdrawal from the cell cycle and commitment to terminal differentiation. Some of the genetic pathways underlying these events are beginning to be elucidated, however, the exact molecular events remain to be determined. In this review, we summarize the involvement of several signaling pathways in different stages of epidermal morphogenesis.