Skin is considered as the border defining the limits of the body from the external world and functions as a barrier between the two. In this capacity, it has evolved to be an integral part of the innate and adaptive immune system. Although many reviews have described skin inflammation and processes that lead to its clinical manifestations, we are not aware of any reviews that have focused on immunologic activity occurring in the absence of any visual inflammatory cues. In this review, we discuss the importance of subclinical inflammation in human skin and its relevance to innate immune surveillance under physiologic conditions. Reactive oxygen species generated by metabolic processes, ultraviolet radiation or oxidizers may damage cells, initiating proinflammatory cascades. In addition to serving as structural skin components, keratinocytes have significant immunologic activity: they secrete proinflammatory cytokines and mediators, including interleukin (IL)-1α, IL-6, IL-10, tumor necrosis factor-α and granulocyte-macrophage colony-stimulating factor. Infant skin is particularly susceptible to irritation, inflammation and infection, since skin barrier function is not fully developed after birth and continues to mature throughout the first few years of life. Non-invasive methods such as fluorescence spectroscopy, spectral imaging and diffuse reflectance spectroscopy, as well as minimally invasive tape stripping, can be used to assess subclinical inflammatory markers in vivo, including erythema, epidermal cell proliferation rate and cytokine concentrations. Appropriately formulated skin care products may help maintain skin barrier integrity and enhance its capacity. In the future, assessment of subclinical inflammation may help clinicians prevent acute or chronic inflammatory conditions of the skin.