Glaucoma is a major cause of vision loss worldwide with nearly 8 million people bilaterally blind from the disease. This number is estimated to increase over the next years. The key to preventing blindness from glaucoma is effective diagnosis and treatment. The classical glaucoma treatment focuses on IOP reduction. Increased IOP is indeed an undisputable risk factor for the development and progression of Glaucomatous Optic Neuropathy (GON). But there is mounting evidence in literature that other risk factors are involved as well. These additional factors may by themselves lead to GON or they may render the eye more sensitive to IOP. Among the most often described factors are: Flammer-syndrome, low blood pressure, increased retinal venous pressure, oxidative stress. Better knowledge of the pathogenesis has opened up additional therapeutical approaches often called non-IOP lowering treatment. Whilst most of these new avenues of treatment are still in the experimental phase, others are already used by some physicians. Non-IOP lowering treatment includes improvements of ocular blood flow, particularly blood flow regulation. This can be achieved by improving the regulation of ocular blood flow (improving auto regulation) by drugs such as carbonic anhydrase inhibitors, magnesium or calcium channel blockers. These drugs also in part decrease increased retinal venous pressure in the eyes of patients. Increased retinal venous pressure decreases perfusion pressure in the patients’ eyes and thus increases the risk of glaucomatous progression. The patients’ blood pressure also needs to be monitored carefully as low blood pressure, particularly nocturnal over dips or blood pressure fluctuations, increase the risk of further damage. Blood pressure can be increased by an increase in salt intake or in rare cases by treatment with fludrocortisone. Reduction of oxidative stress, especially at the level of mitochondria, also seems to be protective. This can be achieved by gingko or foods rich in polyphenolic flavonoids.This review describes the individual mechanisms which may be targeted by non-IOP lowering treatment.