Dry eye disease (DED) is a common condition with signs and symptoms that vary depending on a wide range of environmental factors to which people are exposed in their daily lives. Factors such as variable temperature, airflow velocity, relative humidity, seasonality, and pollutants can alter the rate of tear film evaporation, improving or exacerbating symptoms of DED. Results from currently available clinical tests do not always correlate well with patient-reported symptoms, and the continually changing environment and variability in DED symptoms present challenges for the design and conduct of clinical trials. Controlled adverse environment chambers allow standardization of temperature, humidity, and airflow and may minimize potential confounding factors in clinical investigations. Their use can promote accurate study of the pathophysiology of DED, discovery of disease biomarkers, and assessment of the effect of various therapeutic approaches on patients’ symptoms. Controlled adverse environment chambers have been used to simulate indoor surroundings such as airplane cabins and to test their effects on contact lens wearers. This review summarizes how these chambers may be useful for the development, approval, and differentiation of potential new treatments for DED.