Dry eye, an age-related condition, is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability. Environmental factors are also often implicated in dry eye including exposure to pollutants, ultraviolet (UV) radiation and ozone as well as the chronic use of preserved eyedrops such as in the treatment of glaucoma. These factors increase oxidative stress and ocular surface inflammation. Here, we reviewed the cellular, animal and clinical studies that point to the role of oxidative stress in dry eye disease. The biomarkers used to indicate oxidative damage in ocular surface tissues include 8-hydroxy-2 deoxyguanosine (8-OHdG), 4-hydroxynonenal (HNE) and malondialdehyde (MDD). Antioxidative defences in the ocular surface occur in the form of tear proteins such as lactoferrin and S100A proteins, and enzymes such as superoxide dismutase (SOD), peroxidase, catalase and mitochondrial oxidative enzymes. An imbalance between the level of reactive oxygen species (ROS) and the action of protective enzymes will lead to oxidative damage, and possibly inflammation. A small number of interventional studies suggest that oxidative stress may be directly targeted in topical therapy of dry eye treatment. For example, in vitro studies suggest that L-carnitine and pterostilbene, a blueberry component may reduce oxidative stress, and in animal studies, alpha-lipoic acid (ALP) and selenoprotein P may be helpful. Examples of treatments used in clinical trials include vitamin B12 eyedrops and iodide iontophoresis. With recent emphasis on ageing medicine and preventive holistic health, as well as the role of environmental science, research on oxidative stress in the ocular surface is likely to have increasing impact in the coming years.