Transepidermal water loss (TEWL) is widely used to assess and quantify skin insensible water loss to assess skin's barrier function integrity. Low TEWL values are normally indicative of intact skin and a healthy functional barrier, whereas an increased TEWL reveals a disturbed or disrupted skin barrier. Because most skin sites at which these measurements are made have eccrine glands present, the contribution of the sweat gland activity to these measurements is variable and, in most cases, unknown. The separation between the contribution of water loss that is reflective of the skin barrier integrity versus that contributed via eccrine activation is not easy and is made more difficult since both components increase with increasing skin and environmental temperature. Endogenous factors that impact eccrine sweat gland activity include sympathetic nervous system activity, emotional stress, physical activity, eccrine gland density, and age. Exogenous factors that impact eccrine gland activity include ambient temperature and humidity and the climate where one resides. The aforementioned variables impact eccrine gland activity positively or negatively and therefore alter TEWL values accordingly. Although it may be theoretically possible to control all these factors, the difficulty in doing so results in only a few being controlled during most TEWL measurements. Such confounding processes may have impacted historical TEWL reference ranges and values previously reported. Thus, the impact of eccrine activation on standardly measured TEWL values is at this juncture unclear and may be a component contributing to some reported variability in TEWL values. To help clarify the issues, a literature review was conducted to investigate and summarize relevant prior research efforts and outcomes with respect to ways to consider eccrine activity in TEWL measurements and estimate the contribution of eccrine gland activity to TEWL values. Online databases such as Excerpta Medica Database (EMBASE), Public/Publisher Medline (PubMed), Elton B. Stephans Company (EBSCO), Google Scholar, and Wiley Online Library were searched with "transepidermal water loss" or "TEWL" in the title combined with "eccrine glands" or "sweat" anywhere in the text. The present findings indicate a multiplicity of biological and environmental variables impacting eccrine gland activity and thereby potentially affecting measured TEWL values. Even if laboratory conditions adhere to various guidelines and recommendations, it is not yet possible to separate the eccrine activation component from the parameter of true interest in the assessment of the skin's physiological barrier function except for full gland deactivation. The amount that such eccrine gland activation impacts the measured value of TEWL is generally not determined using currently available methods and the only sure way to eliminate a confounding effect is to inactivate the glands during such TEWL measurements. Because such eccrine gland deactivating approach is not usually desirable or even possible, other ...