Primary open-angle glaucoma (POAG) is one of the most significant medico-social problems in the modern society. The development of its refractoriness aggravates the pathological process and inevitably leads to blindness. Despite the fact that this form accounts for up to 80% of all glaucoma cases, the problem of POAG refractoriness has not been considered in sufficient detail in either Russian or foreign sources. The article presents an overview of the main ophthalmic factors that contribute to changes in various structures of the eyeball and accelerate the formation of refractory forms of POAG. One of the reasons for that is a genetic predisposition to the development of POAG. It is worth noting that in 60% of patients with a family history of glaucoma, the risk of developing POAG increases by 10 times (among the first-degree relatives).Additional factors in the development of the refractory form of POAG are the reactive syndrome and during laser surgery. It is important to emphasize that the risk of development and progression of POAG in patients with a hereditary predisposition is much higher, while indicating a number of therapeutic measures may lead to drug resistance. Genotyping is a promising scientific and practical direction of research, allowing prediction of the pharmacological response to a particular drug and individual selection of the appropriate therapy according to the patient's genotype. This approach could help prevent a number of complications and improve the accuracy of disease prognosis.