This article reviews the risk factors, clinical presentation and therapies that have been investigated for non-arteritic anterior ischaemic optic neuropathy (NAAION). Additionally, it provides an update from recent rodent and primate models, offering a new insight into the pathophysiology of this disease and providing a platform for potential treatment trials. The authors successfully illustrate the current proposed mechanisms and risk factors for NAAION, including a small cup-to-disc ratio, so-called ‘disc-at-risk’, optic nerve head (ONH) drusen, increasing age, systemic and ocular hypertension, episodic hypotension, i.e. nocturnal or perioperative, and cardiovascular profile co-morbidities, such as hypercholesterolaemia, diabetes mellitus, obstructive sleep apnoea and also medication, i.e. phosphodiesterase type 5 inhibitors for erectile dysfunction. The most widely accepted pathogenic theory is that NAAION results from dysfunction of vascular homeostasis or autoregulation at the optic nerve head, following a sequence of events including subclinical reduction in blood flow, hypoxia, axonal oedema leading to acute compartment syndrome and vascular infarction of nerve tissue – typically segmental – commonly associated with nerve fibre layer haemorrhages and resulting in altitudinal visual field scotomata. A typical case of NAAION is presented, followed by discussion around the findings of the Ischaemic Optic Neuropathy Decompression Trial (IONDT) and the natural history of NAAION. The lifetime risk for second eye involvement is estimated at 30-40%. Previous studies have shown that there may be a role of corticosteroids in the treatment of NAAION in the acute phase, with faster resolution of disc oedema and higher rates of visual acuity and visual field improvement. The largest retrospective studies, including IONDT, have failed to show a protective benefit of Aspirin for the fellow eye. Various neuroprotective agents have also been studied in the acute NAAION phase, such as hyperbaric oxygen, topical brimonidine and Levodopa, with no clear benefit from any of them, apart from possibly the latter. Finally, this review article focuses on the current rodent and primate animal models (rats and rhesus monkeys) to investigate experimental NAAION induction with resulting effects of axonal damage via histologic examination and gene expression analysis. The described sequence of events includes disruption of cell architecture in the laminar region of the optic nerve, upregulation of inflammatory components (complement, tumour-necrosis-factor-receptor-1, cathepsin-L and oestrogen-response-gene EET-1), loss of optic nerve oligodendrocytes and microglia and furthermore loss of retinal ganglion cells (RGC) with sparing of other retinal layers, but breakdown of the blood-brain barrier. Novel neuroprotective agents were studied through the afore-mentioned animal models, such as ciliary-derived neurotrophic factor (CNTF) and prostaglandin J2 (PGJ2), demonstrating activation of anti-apoptotic pathways, preservation of RGC density and RGC axons, myelination of the post-laminar optic nerve and reduction of ONH oedema. The authors conclude by reminding us of the fact that a certain percentage of NAAION patients will improve spontaneously and that most therapeutic trials have significant limitations and are often non-randomised, whereas we are still lacking reliable treatment options of proven efficacy.