Glaucoma, a group of optic neuropathies, is one of the leading causes of irreversible blindness in the world. It is characterized by degeneration of the optic nerve and progressive visual field loss, often associated with elevated intraocular pressure (IOP). In primary open-angle glaucoma, the most common form of the disease, IOP occurs as a result of abnormally increased resistance to drainage of aqueous humor through the conventional outflow system, which comprises the trabecular meshwork and the Schlemm's canal. The pharmacological treatment of glaucoma has been classically aimed at lowering elevated IOP, either decreasing the production of aqueous humor or improving its outflow. Increasing knowledge of trabecular meshwork physiology shows that this tissue has unique morphologic and functional properties involved in the regulation of aqueous humor outflow. Although trabecular meshwork physiology is yet to be fully revealed, ion channels involved in cell contractility or cell volume regulation, or those capable of responding to high pressure, have been described and may be considered promising pharmacological targets for the treatment of glaucoma. The cytoskeleton architecture of the trabecular meshwork cell is thought to be an important regulator of aqueous humor outflow. Gene technology directed at discovering genes linked to the development of glaucoma or to those upregulated in response to elevated IOP is challenging research but provides an insight into future gene therapy. New tools to study trabecular meshwork physiology have recently been developed, including the use of lentivirus for gene delivery or fusion proteins with a protein transduction domain. These vectors are targeted specifically to the trabecular meshwork and are powerful techniques with broad applications for future gene therapy or as new forms of drug delivery.