Infectious Spleen and Kidney Necrosis Virus (ISKNV) is a very infectious virus with a large host range that includes over 50 freshwater and marine fish species and causes explosive and high-level mortality in those fish. It causes immune suppression and tissue damage, mainly targeting the spleen and kidney. ISKNV also poses serious economic threats to aquaculture globally, particularly in tropical areas. It is diagnosed predominantly by PCR and immunological techniques, while treatment is not effective. Prevention is dependent upon biosecurity, sound husbandry, and prompt detection. Constant vaccine development provides a promise of potential future control, so disease management is essential for sustainable aquaculture.