ABSTRACTMegalocytivirus, a large double‐stranded DNA virus belonging to the Iridoviridae family, has infected over 100 species of fish, leading to significant economic losses in the aquaculture, food, and ornamental fish industries. These viruses exhibit icosahedral symmetry and have diameters ranging from 120 to 200 nm. Two distinct viral species of genus Megalocytivirus have been identified: Megalocytivirus pagrus 1 and Megalocytivirus lates 1. Megalocytivirus pagrus 1 encompasses three distinct genotypes: infectious spleen and kidney necrosis virus, red seabream iridovirus, and turbot reddish body iridovirus, whereas Megalocytivirus lates 1 comprises a single genotype, known as scale drop disease virus. Infection with Megalocytivirus pagrus 1 is a notifiable disease to the World Organisation for Animal Health. Over the past two decades, significant progress has been made in various aspects of megalocytivirus biology, including the understanding of its molecular genetics, transmission modes, host ranges, pathogenic mechanisms, diagnostic methodologies, and vaccines. This review provides a comprehensive overview of the current understanding of megalocytiviruses, focusing on its epidemiology, pathogenicity, immune evasion, and prevention strategies for fish infected with megalocytiviruses. We hope that these findings will provide new insights in the development of effective prevention and control strategies for megalocytiviral diseases.