The article reviews the role of skin immune cells in maintaining skin health and addressing diseases. It highlights the importance of keratinocytes as sensors of danger through the activation of inflammasomes and the role of CD103+ dendritic cells in cross-presenting skin-tropic pathogens. The review also emphasizes the significance of tissue-resident T cells in skin homeostasis and pathology, rather than circulating T cells. Key findings include the activation of keratinocytes by pathogens and environmental insults, leading to the production of antimicrobial peptides and pro-inflammatory cytokines. The article discusses the functions of Langerhans cells, keratinocytes, γδ T cells, and skin-resident T cells, as well as the role of unconventional T cells in skin inflammation and carcinogenesis. It concludes with insights into the immunopathogenesis of psoriasis and the potential for new therapeutics targeting skin immune sentinels.The article reviews the role of skin immune cells in maintaining skin health and addressing diseases. It highlights the importance of keratinocytes as sensors of danger through the activation of inflammasomes and the role of CD103+ dendritic cells in cross-presenting skin-tropic pathogens. The review also emphasizes the significance of tissue-resident T cells in skin homeostasis and pathology, rather than circulating T cells. Key findings include the activation of keratinocytes by pathogens and environmental insults, leading to the production of antimicrobial peptides and pro-inflammatory cytokines. The article discusses the functions of Langerhans cells, keratinocytes, γδ T cells, and skin-resident T cells, as well as the role of unconventional T cells in skin inflammation and carcinogenesis. It concludes with insights into the immunopathogenesis of psoriasis and the potential for new therapeutics targeting skin immune sentinels.