Many unfavorable stress conditions, such as wounding, drought, extreme temperatures, salinity and pathogen attacks, control growth, development and plant yield. To survive in such environments, plants have developed many strategies. They are able to induce the expression of a large number of genes that encode effectors, receptors, as well as signaling proteins and protective molecules. Among all, pathogenesis-related proteins (PRs) were found to be activated in response to different biotic and abiotic threats. Those proteins have a wide range of functions; acting as chitinases, peroxidases, anti-microbial agents, hydrolases, protease inhibitors, and other activities. Activation of PR proteins has been demonstrated in different plant families as a response to different stresses. In this review, we have summarized the structural, biological and functional characteristics of the different PRs families in plants, their regulation, as well as their roles in plant defense against abiotic and biotic stresses.