Background: As atmospheric greenhouse gas concentrations continue to rise, temperature and humidity will increase further, causing potentially dire increases in human heat stress. On physiological and biophysical grounds, exposure to higher levels of humidity should worsen heat stress by decreasing sweat evaporation. However, population-scale epidemiological studies of heat exposure and response often do not detect associations between high levels of humidity and heat-related mortality or morbidity. These divergent, disciplinary views regarding the role of humidity in heat-related health risks limit confidence in selecting which interventions are effective in reducing health impacts and in projecting future heat-related health risks. Objectives: Via our multidisciplinary perspective we seek to a) reconcile the competing realities concerning the role of humidity in heat-related health impacts and b) help ensure robust projections of heat-related health risks with climate change. These objectives are critical pathways to identify and communicate effective approaches to cope with present and future heat challenges. Discussion: We hypothesize six key reasons epidemiological studies have found little impact of humidity on heat–health outcomes: a) At high temperatures, there may be limited influence of humidity on the health conditions that cause most heat-related deaths (i.e., cardiovascular collapse); b) epidemiological data sets have limited spatial extent, a bias toward extratropical (i.e., cooler and less humid), high-income nations, and tend to exist in places where temporal variations in temperature and humidity are positively correlated; c) analyses focus on older, vulnerable populations with sweating, and thus evaporative, impairments that may be further aggravated by dehydration; d) extremely high levels of temperature and humidity (seldom seen in the historical record) are necessary for humidity to substantially impact heat strain of sedentary individuals; e) relationships between temperature and humidity are improperly considered when interpreting epidemiological model results; and f) sub-daily meteorological phenomena, such as rain, occur at high temperatures and humidity, and may bias epidemiological studies based on daily data. Future research must robustly test these hypotheses to advance methods for more accurate incorporation of humidity in estimating heat-related health outcomes under present and projected future climates. https://doi.org/10.1289/EHP11807