Corneal edema as a postoperative complication is common to many ophthalmic procedures, given that trauma to cells, direct or indirect, and inflammation is largely unavoidable. The magnitude of this loss of endothelial integrity, either in the short term or long term, dictates whether corneal edema becomes clinically apparent or symptomatic. Recently, an observed accelerated rate of endothelial cell loss noted after postmarket surveillance has resulted in the recall and discontinuation of certain therapeutic ocular devices. Notably, in 2017, the CyPass supraciliary minimally invasive glaucoma surgery device was approved by the US Food and Drug Administration based on its safety and efficacy demonstrated in a 2-year randomized clinical trial, the Study of an Implantable Device for Lowering Intraocular Pressure in Glaucoma Patients Undergoing Cataract Surgery (COMPASS; NCT01085357).1 In 2018, however, the device was voluntarily discontinued after a 5-year analysis of participants in the original trial, A Study to Assess Long-Term Safety of the CyPass Micro-Stent in Patients Completing the COMPASS Trial (COMPASS XT; NCT02700984), revealed a significantly higher endothelial cell loss in the group receiving both phacoemulsification and CyPass microstenting, compared with the group who received phacoemulsification alone. It is vitally important to understand the pathogenesis of glaucoma procedure–associated endothelial cell loss as a means for understanding the prognostic factors in a certain glaucoma procedure’s success. The literature examining corneal edema after glaucoma interventions report differing causative mechanisms, including 3 main plausible mechanisms: mechanical trauma, change in composition of aqueous humor, and change in the flow of aqueous humor dynamics. Recognizing risk factors and understanding causative mechanisms for endothelial cell loss after glaucoma surgery would potentially minimize this sight-threatening complication through changes in surgical interventions and the design of future devices.