Zebrafish (Danio rerio) share high genetic and physiological similarity with mammals and possess complex phenotypes in all major, evolutionarily conserved, neurobehavioral domains. Zebrafish are also rapidly emerging as a promising novel model organism in neuroimmunology and psychoneuroimmunology research. Here, we summarize neuroimmune mechanisms and their experimental modulation in zebrafish, and discuss some other relevant physiological aspects, such as the gut microbiota-brain interplay, as well as the translational insights from zebrafish neuroimmune models. © 2023 Elsevier Inc. All rights reserved.