Peipei Zhang,1,2 Yan Su,1,2 Fang Liu1,2 1Shanghai Tenth People's Hospital of Tongji University, Shanghai, People's Republic of China; 2Wenzhou Ophthalmology and Optometry Hospital, Wenzhou Medical College, Wenzhou, People's Republic of China Abstract: Age-related macular degeneration, pathologic myopia, ocular trauma, and other eye diseases can cause choroidal neovascularization (CNV). In recent years, photodynamic therapy (PDT), anti-vascular endothelial growth factor (anti-VEGF) medications, laser treatment, and other measures against CNV have been gradually applied in the clinical setting and in some cases have achieved good results. However, the pathogenesis of CNV has not been fully elucidated. The costimulatory system made up of cluster of differentiation 40 protein (CD40) and its ligand (CD40L) is an important signal transduction pathway among immune cells. The activation of CD40 can also stimulate the secretion of a variety of angiogenic growth factors (eg, VEGF) and basic fibroblast growth factors that might lead to CNV. The high level expression of CD40 and CD40L has been detected in CNV diseases. Interference with the CD40 signaling pathway may become a new target for CNV treatment. We review the relationship between CD40, CD40L, and CNV. Keywords: choroidal neovascularization, NV, CD40, angiogenesis factor