Plants are sessile; they cannot move to avoid adverse environmental conditions. Pathogenesis-related (PR) proteins are induced in the plant by imposing different biotic stresses such as pathogens and abiotic stresses like drought, cold, salinity, heavy metal etc. There are currently nineteen families of PR proteins (PR-1 to PR- 19), with 17 confirmed and two putative PR families identified and classified based on their biochemical nature. PR proteins promote innate resistance in plants by disintegrating fungal cell walls, permeabilizing membranes, suppressing transcription, and inactivating ribosomes. Previous research has shown that they play an important role in determining resistance to phytopathogens, making them a promising candidate for developing disease-resistant crop varieties. Plant genetic engineering could be used to create disease-resistant transgenic crops by utilizing several PR genes (thaumatin, osmotin-like proteins, chitinases, glucanases, defensins, thionins, oxalate oxidase, oxalate oxidase-like proteins/germin-like proteins, and LTPs). In this review, we attempt to demonstrate the types and biochemical nature of various PR proteins, as well as their insight mechanism for pathogen resistance and the use of PR proteins for disease-tolerant plants developed at a low cost.