Betanodavirus is the etiological agent of viral nervous necrosis (VNN), also known as vacuolating encephalopathy and retinopathy (VER) or encephalomyelitis, which is a devastating viral disease affecting marine and freshwater sh species worldwide. First observed in 1986 on an aquaculture farm of Japanese parrotsh (Calotomus japonicus) in Nagasaki, Japan, VNN was linked to loss of balance, necrosis in the brain and retina, and death of sh fry (of 6-25 mm length) during the summer (June-July) . Almost simultaneously, VNN was discovered in Australia, Norway, and France, involving barramundi (Asian sea bass, Lates calcarifer), turbot (Scophthalmus maximus), European sea bass (Dicentrarchus labrax), red-spotted grouper (Epinephelus akaara), striped jack (Pseudocaranx dentex) [2-5], and other cultured warm-water and cold-water marine sh species (n = 30) throughout the world . Given its capacity to induce high mortality (80%–100%) in juvenile sh, VNN exerts huge economic and ecological burdens on aquaculture industry and wild marine species . In this chapter, we focus on betanodavirus in relation to its taxonomy, morphology, genome structure, epidemiology, clinical features, pathogenesis, diagnosis, and control, together with stepwise molecular protocols for its i dentication and diagnosis.