Plants use a plethora of sophisticated detection systems to recognize a variety of attackers and to subsequently initiate defense responses. A well-known paradigm in this context is the perception of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs), a process referred to as pattern triggered immunity (PTI). Additionally, plants also recognize endogenous molecules to induce similar defense responses. These molecules are believed to be released upon enemy attack and are therefore referred to as danger-associated molecular patterns (DAMPs). The best-investigated DAMP so far is systemin, a short peptide capable of inducing defense responses in tomato and required for full-strength defense against insect herbivores. More recently, a family of eight peptides has been discovered in Arabidopsis, named Arabidopsis thaliana danger peptides (AtPeps) 1-8. These AtPeps have been shown to be capable of inducing PTI-like responses and to be expressed upon the detection of various biotic stresses, therefore being considered as DAMPs. Moreover, two PRRs, named Pep-Receptor 1 (PEPR1) and Pep-Receptor 2 (PEPR2) have been identified to perceive AtPeps and to induce defense responses upon receptor-ligand interaction. Despite of eliciting PTI responses and being expressed upon the detection of biotic stress, no direct beneficial involvement of the AtPep-PEPR system to plant defense against attackers has been described so far. Taking advantage of a mutant deficient in both PEPRs and thus fully impaired in AtPep-PEPR signaling, we investigated the potential contribution of a functional AtPep-PEPR system to plant defense responses. In a first approach, we investigated the potential interplay between MAMP and DAMP signaling, especially in the context of DAMPs being believed to act as endogenous amplifiers of MAMP-induced PTI. Doing so, we identified that the AtPep-triggered production of reactive oxygen species (ROS) is strongly enhanced upon previous MAMP detection, indeed indicating a role of the AtPep-PEPR signaling system as an enhancer of MAMP-triggered defense signaling. In a second approach, we compared the AtPep-PEPR system to systemins – well described DAMPs in tomato with generally similar molecular features to AtPeps. Following up the lead that systemins are important mediators of defense responses against herbivorous insects, we checked whether a similar role would apply to the AtPep-PEPR system. Here, we could show that the AtPep-PEPR system is indeed induced by herbivore feeding and strongly interacts with the plant hormone jasmonic acid (JA) to orchestrate defense responses. Accordingly, mutants deficient in AtPep-PEPR signaling are strongly impaired in defense responses against the generalist herbivore Spodoptera littoralis, underlining the importance of AtPep signaling in plant defense against herbivores. Thirdly, we followed up a lead that the expression of some AtPeps as well as both PEPRs is induced upon virus infection. Assessing the potential contribution of the AtPep-PEPR system to plant defense against viruses, we could not observe an increased susceptibility of plants deficient in both PEPRs. However, mutants in BAK1 (BRI1 Associated Kinase 1), a co-receptor required for full-strength AtPep-triggered signaling and many other PRRs, showed a clearly increased susceptibility to all viruses tested. Therefore, we established a first potential line of evidence for a role of PTI in plant defense against viruses. All in all, we provide several lines of evidence that show the contribution of a functional AtPep-PEPR signaling system to plant defense. Therefore, we underline the pivotal importance of DAMP signaling to plant immunity against a plethora of biotic invaders.