The skin serves as a front line of defense against harmful environmental elements and thus is vital for organismal survival. This barrier is comprised of a water-tight epithelial structure reinforced by an arsenal of immune cells. The epithelial and immune components of the skin are interdependent and actively dialogue to maintain health and combat infectious, injurious, and noxious stimuli. Here, we discuss the molecular mediators of this crosstalk that establish tissue homeostasis and their dynamic adaptations to various stress conditions. In particular, we focus on immune-epithelial interactions in homeostatic tissue regeneration, during natural cycling of the hair follicle, and following skin injury. We also highlight the epithelial derived factors that orchestrate immunity. A comprehensive and mechanistic understanding of dynamic interactions between cutaneous immune cells and the epithelium can be leveraged to develop novel therapies to treat a range of skin diseases and boost skin health.