Plant-parasitic nematodes, particularly the sedentary endoparasitic forms, are cosmopolitan pests, collectively causing over $100 billion in annual crop loss worldwide. In the past decade, significant progress has been made in identifying genes and their products that define key aspects of the host–parasite interface, including enzymes and proteins with direct roles in virulence and resistance. However, little remains known about how a host is identified or how the development of the nematode is coupled to establishment of the parasitic interaction. Here, we consider the role of signaling molecules and their interplay with nematode development from hatch through primary interaction with the plant.