The skin, situated at the critical juncture between the host and the environment, is subject to a variety of potentially damaging agents including microbial organisms, toxins, and gene-altering radiation. Diverse immunocytes, including those resident in the skin and those with the capacity to traffic to and from the skin, direct two major types of immune responses: more immediate and less discriminate defenses (so-called innate immunity), and more coordinated and antigen-specific responses (so-called adaptive immunity). This review will focus on features of the adaptive immune system operative within the skin and consider the roles of dendritic cells, lymphocytes, endothelial cells, chemokines, and cytokines. In particular, the major subsets of T cells and the mechanisms by which they endow and regulate the features of adaptive immunity in the skin will be considered, including: the efficient surveillance and recognition of diverse foreign-antigens while limiting reactivity against self-antigens; differentiation into various effector cells capable of inducing apoptosis of infected/damaged cells and/or directing the activities of other immunocytes; and providing for immunologic memory whereby subsequent antigen exposure elicits a rapid and augmented antigen-specific response. It is within this context that the adaptive immune system will be considered for its role in the skin in mediating microbial defense with direct relevance to tumor immunosurveillance and inflammatory disease.