The skin is a protective interface between internal organs and the environment; it is the largest tissue of the human body. However, the skin does not serve merely as a physical barrier. It is also an active immune organ, traversed by a network of lymphatic and blood vessels. This immunologic structure contains immunologic cells such as T lymphocytes, Langerhans cells (LCs), dendritic cells, and keratinocytes. Langerhans cells represent the cutaneous counterpart of dendritic cells. LCs not only act as professional antigen-presenting cells to induce antigen-specific T cells for adaptive immune responses, but they also initiate a cascade of innate immune responses by antigenic stimulus such as transplant tissue. In transplantation immunology, either donor or recipient LCs fulfill an important mission in rejection or acceptance of donor tissue. Vascularized or nonvascularized skin allografts may create an immunologic response through different pathways. In both transplant models, skin diameter may change antigenic load, thereby determining rejection or acceptance response. This article discusses the effects of the cellular component in the skin immune system on immunologic responses of vascularized or nonvascularized skin allografts and describes the differences between the two immunologic cascades.