It is well recognized that bacteria communicate via small diffusible molecules, a process termed quorum sensing. The best understood quorum sensing systems are those that use acylated homoserine lactones (AHLs) for communication. The prototype of those systems consists of a LuxI-like AHL synthase and a cognate LuxR receptor that detects the signal. However, many proteobacteria possess LuxR receptors, yet lack any LuxI-type synthase, and thus these receptors are referred to as LuxR orphans or solos. In addition to the well-known AHLs, little is known about the signaling molecules that are sensed by LuxR solos. Here, we describe a novel cell–cell communication system in the insect and human pathogen Photorhabdus asymbiotica . We identified the LuxR homolog PauR to sense dialkylresorcinols (DARs) and cyclohexanediones (CHDs) instead of AHLs as signals. The DarABC synthesis pathway produces the molecules, and the entire system emerged as important for virulence. Moreover, we have analyzed more than 90 different Photorhabdus strains by HPLC/MS and showed that these DARs and CHDs are specific to the human pathogen P. asymbiotica . On the basis of genomic evidence, 116 other bacterial species are putative DAR producers, among them many human pathogens. Therefore, we discuss the possibility of DARs as novel and widespread bacterial signaling molecules and show that bacterial cell–cell communication goes far beyond AHL signaling in nature. Significance Bacteria can communicate with each other by small diffusible molecules, a process termed quorum sensing. Many bacteria use acylated homoserine lactones (AHLs) as signals, which are sensed by so-called LuxR-type receptors. With the photopyrones from the insect pathogenic bacterium Photorhabdus luminescens , we recently identified the first quorum sensing molecules different from AHLs that are sensed by a LuxR-type receptor. Here we describe the second novel quorum sensing molecule sensed by a LuxR-type receptor of Photorhabdus species, PauR of the human pathogen Photorhabdus asymbiotica . We demonstrate that P. asymbiotica communicates via dialkylresorcinols (DARs) and cyclohexanediones (CHDs). As the synthesis pathway is widespread, and often present in human pathogens, we discuss DARs and CHDs as novel and widespread signaling molecules.