Trabecular meshwork (TM) cells likely play a key role in regulating outflow facility and hence intraocular pressure. They function in a dynamic environment subjected to variations in mechanical and fluid shear forces. Because the extent of mechanical stress on the trabecular meshwork is dependent on the intraocular pressure, the behavior of TM cells under mechanical strain may suggest mechanisms for how outflow facility is regulated. Studies have demonstrated that TM cells respond in a variety of ways to mechanical loads, including increased extracellular matrix turnover, altered gene expression, cytokine release, and altered signal transduction. This review highlights some of the considerations and limitations of studying the mechanobiology of TM cells.