Nematodes represent the most abundant group of metazoans on earth. They utilize diverse chemicals to interact with con-specific and hetero-specific organisms, and are also impacted by compounds produced by other interacting organisms. In the first part of this review we discuss how nematode-derived glycolipids modulate their behavior and development, as well as the interactions with other organisms. Furthermore, we provide a short overview about other secondary metabolites produced by nematodes that affect different life traits of free-living nematodes. In the second part of this review we discuss how different bacteria-, nematode-, and plant-derived chemicals such as volatile organic compounds, root exudates, and plant defenses regulate the interaction between entomopathogenic nematodes, their symbiotic bacteria, insect prey, predators, and plants.