The therapeutic response of anti-vascular endothelial growth factor (VEGF) differs among individuals. According to the changes of central retinal thickness, intraretinal fluid, subretinal fluid, best corrected visual acuity and other morphological or functional manifestations after treatment, the performance of the treated eyes can be classified as optimal response, poor response and non-response. A variety of factors could account for poor or non-response to anti-VEGF, such as genomic polymorphism and specific genomic risk alleles, lesion characteristics, vitreous and macular structural abnormalities, resistance to anti-VEGF drug, and the role of pericytes and others. The common counter measures include increasing the dosage, shortening the injection interval and replacing with another alternative drug, inhibition of pericytes, relieving vitreomacular anatomical abnormalities. It is still worthy of further exploration that how to assess individual reasons for non-response, so that we can give proper treatment to reduce the excessive use of anti-VEGF drugs and improve the clinical management of ocular neovascularization diseases.