The innate immune response is evoked as a consequence of interactions between invading foreign infectious agents and host immune cells. A successful innate immune response is pivotal in maintaining the delicate balance between health and disease; an insufficient response results in infection, whereas an excessive response results in prolonged inflammation and tissue damage. Alterations in the state and function of the nervous system influence the immune response. The nervous system regulates innate immune responses through the release of neurotransmitters, neuropeptides and neurohormones. However, many questions related to the molecular and cellular mechanisms involved, the physiological role of the link between the immune and the nervous system, and the biological significance of neuro-immune interactions remain unresolved. The interactions between the nematode Caenorhabditis elegans and its pathogens provide insights into mechanisms of neuroendocrine regulation of immunity and address many outstanding issues related to neuro-immune interactions.