Choroidal neovascularization (CNV) is a major cause of severe vision loss in patients with age-related macular degeneration. Despite intensive research, the pathogenesis of choroidal neovascularization is still poorly understood. Many factors were identified to be involved in the development of choroidal neovascularization. Choroidal blood flow and hemodynamic changes with consecutive impairment of the perfusion, especially of the choriocapillaris, as well as reduction of clearance of debris from the retinal pigment epithelium and Bruch’s membrane were proposed to play a role. Imbalance of the angiogenic process including different factors such as vascular endothelial growth factor, angiopoietins, basal fibroblast growth factor and pigment epithelium-derived factor as well as degradation of extracellular matrix are also important factors for the development of CNV. Transgenic and knockout studies have provided important insights into the development of CNV, the main cause of vision impairment and loss in patients with age-related macular degeneration.