The skin is one of the largest organs in the human body, which acts as the primary interface with the external world. In view of its protective role, mammalian skin consists of physical and immunological barriers. The water-impermeable stratum corneum and the tight junctions in the granular layer work at the epidermal level work as the most important first and second “physical” barriers. Upon antigen invasion to the skin, the integrated innate and acquired immune systems in both the epidermis and dermis are activated in a coordinated manner to neutralize the external intruder as the strong third “immunological” barriers. Dendritic cells and macrophages are known to play pivotal roles in such immunological barriers. Intra-vital analysis of the murine skin by two-photon microscopy enabled us to assess the habituate and the direct interactions of various cells in the skin in situ, which reside or infiltrate upon inflammation. We introduce the recent works how dendritic cells and macrophages orchestrate the skin immunity, highlighting the importance of sequential leucocyte cluster formation in the efficient activation of memory T cells in the skin, which can be attributed as ‘inducible skin-associated lymphoid tissue (iSALT)’.