The epidermis is a stratified epithelium that functions as a barrier protecting the organism from dehydration, mechanical trauma, and microbial insults. This barrier function is established during embryogenesis through a complex and tightly controlled stratification program. Whereas the morphological changes that occur during epidermal development have been extensively studied, the molecular mechanisms that govern this process remain poorly understood. In this review we summarize the current advances that have been made in understanding the molecular mechanisms that regulate epidermal morphogenesis.