Most organisms can secrete pheromones to mediate their behavior, development, and physiological metabolism. However, prior to the discovery of a group of intra-specific chemical signal substrates called ascarosides the pheromones of nematodes had not yet been described. The main chemical structures of ascarosides are made up of the sugar ascarylose, which is linked to fatty acid-like side chains of varying lengths. Ascarosides were originally isolated from the parasitic nematodeAscaris, the animal after which the group of compounds was named. Ascarosides play important roles in mediating different behaviors and development, such as mate finding, aggregation, and diapause in the free-living species Caenorhabditis elegans. Ascarosides also mediate distinct nematode behaviors, such as retention, avoidance, and long-range attraction. Likewise, a growing body of literature reports the identification of ascarosides in a wide range of other nematodes. The different nematode species respond to distinct, but overlapping, sets of ascarosides.A wide range of biological functions is facilitated by a great diversity of ascarosides with varying chemical structures. Different ascarosides or combinations of ascarosides mediate the production of different phenotypes, and even small differences in chemical structures are often associated with strongly altered activity profiles. Additional complexity arises from concentration-dependent effects, and synergism between different ascarosides. At picomolar concentrations, a synergistic mixture of at least three ascarosides produced by hermaphrodites triggers male-specific attraction inC. elegans. At higher concentrations, the same ascarosides, perhaps in a different mixture, induce the developmentally arrested stage known as dauer. Ascaroside signaling communicates detailed information about the life history and metabolic state of a nematode individual. The production of ascarosides is strongly dependent on environmental conditions, with the expression and concentrations of different ascarosides being sensitive to life stage, sex, food availability, and other environmental factors, suggesting that ascarosides regulate the overall life cycle of C. elegans. At the same, in some studies investigating the ascarosides of parasitic nematodes, most of the species produce species-specific ascaroside mixtures, e.g., ascaroside biosynthesis patterns appear to be correlated with phylogeny. The ascarosides are sensed by several types of chemosensory head neurons, including the ASK, ASI, and ADL neurons, as well as the male-specific CEM neurons. Ascaroside perception is mediated by diverse families of G-protein coupled membrane receptors that act upstream of conserved signal transduction pathways, including insulin/IGF-1 signaling and transforming growth factor beta (TGF-β) signaling. The biosynthesis of ascarosides appears to integrate input from several primary metabolic pathways, including peroxisomal β-oxidation of long-chain fatty acids and amino acid catabolism.In this paper, we reviewed recent discoveries in this field, including reports of the structures and identification, components and functions, biosynthesis and metabolic regulation, allelopathic signaling pathways, and signal regulate mode of ascarosides, not only in nematodes, but also in other organisms. The aim is to provide an updated and comprehensive synthesis of the ascaroside literature. This will benefit future research on the chemical ecology of nematodes, and be of great value to the field of neurobiology.