The epidermis is a barrier for preventing penetration into the skin of pathogens, allergens, toxins and UV radiation. It also avoids the uncontrolled loss of body solutes. Finally, it acts as a mechanical protection. For many years, we are interested in the role of peptidylarginine deiminases (PADs) in the epidermis. Three PADs are expressed in the epidermis, PAD1-3. Their expression/activity is regulated at the transcriptional, translational and posttranslational levels. Whereas the specific role of PAD2 remains enigmatic, PAD1 and PAD3 are involved in the epidermal barrier function, keratins, LL37 anti-microbial peptide, filaggrin and filaggrin-related proteins being the most abundant deiminated epidermal proteins. Deimination promotes the cross-linking of most of them to the cornified envelopes. Furthermore, citrullination of filaggrin is a limiting step in filaggrinolysis, which leads to the production of amino acids and amino acid derivatives essential for proper upper epidermis hydration and plasticity, desquamation, UV protection and epidermal barrier homeostasis. Filaggrinolysis allows the adaptation of keratinocytes to a dry external environment. PAD1 is a regulator of the autophagy process associated with the ultimate step in keratinocyte differentiation. Finally, dysregulation of epidermal citrullination may be involved in the pathogenesis of inflammatory skin diseases, including psoriasis, atopic dermatitis and hidradenitis suppurativa.