Glaucoma is a major cause of blindness in China and the world. Currently, all therapeutic means in treating open-angle glaucoma are limited to control the progression of optic neuropathy by lowering intraocular pressure (IOP). Clinically available medicines lower IOP by either enhancing the uveoscleral pathway or inhibiting aqueous humor production. Since the primary cause of IOP elevation in POAG is elevated outflow resistance in the trabecular outflow pathway, current medicines are not able to correct the underlying pathogenesis and pathophysiology of the disease. In this review article, we discuss a series of new therapeutic targets and therapeutic approaches that are designed to directly modify the pathological changes related to the reduction in trabecular outflow in glaucoma patients. Some of these targets and approaches may produce a significant breakthrough in the treatment of this devastating disease. (Chin J Ophthalmol, 2016, 52: 471-475).