Ocular neovascularization, a common pathological feature of wet age-related macular degeneration (AMD), proliferative and diabetic retinopathy (PDR) leads to fluid and blood leakage, scar formation and ultimately blindness. Elucidation of vascular endothelial growth factor (VEGF) as a key mediator of angiogenesis led to clinically approved anti-VEGF agents. However, these drugs are associated with adverse side-effects, high costs and extensive clinical burden. The phosphatidylinositol-3-kinase (PI3K) pathway is an alternative therapeutic target in angiogenic diseases. The PI3K/Akt/mTOR pathway orchestrates an array of normal cellular processes, including growth, survival and angiogenesis. Here, we review the potential of targeting the PI3K pathway, to treat ocular neovascularization.