Purpose. The development of dry eye therapies requires clinical trial designs to be well-controlled, precise, and reliable. To accomplish this, we must consider proper patient selection, clinically relevant endpoints, and reproducible / predictable study procedures. The Controlled Adverse Environment (CAE) is an established model that controls the many environmental conditions which can influence dry eye for use in the evaluation of dry eye therapeutic agents. The purpose of this paper is to review lessons learned from the thousands of patients who have been evaluated in the CAE. Methods. The CAE standardizes the study of dry eye by regulating humidity (<10%), temperature (76 ± 6 F), airflow (constant, non-turbulent), lighting conditions, and visual tasking (television or PC use). By integrating specific diagnostic equipment such as digital imaging, eye tracking and standardized scales, objective and subjective measures are recorded before, during, and after CAE exposure. This model provides a standard method of challenging all patient eyes equally. Results. After reviewing patient responses in the CAE model, a number of observations have been documented. For example, it has been shown that a patient either exhibit signs only, symptoms only, or both signs and symptoms during exposure to adverse environmental conditions. Compensatory mechanisms such as the ability to reflex tear and blink when the ocular surface is challenged can vary according to the severity and cause of dry eye. Certain endpoints like keratitis, conjunctival redness, tear film stability, fluorophotometry, osmolarity, and the Ocular Protection Index (OPI) are modifiable by environmental conditions while others are not. The effects of influential factors such as age, sex, neural regulation, menopause, and systemic medications known to cause ocular drying have also been investigated in this model. Conclusions. With the use of standardized tools such as the CAE, we are able to maintain an empirical approach towards understanding the various underlying mechanisms of dry eye and evaluating future treatments for this disease.