Catfish industry with an economic impact of $1.9 billion per year and 74% contribution to the finfish production is the largest sector of the U.S. aquaculture. Infectious agents can severely impact catfish production. Catfish viruses such as channel catfish virus (CCV) and blue catfish alloherpesvirus (BCAHV) are problematic during the hatchery and nursery phases of catfish culture. Viruses are dynamic entities that constantly evolve and adapt according to the surrounding environment, available resources, and hosts potentially leading to expansion in host range, host switch, and increase in virulence. Profiling catfish viruses will facilitate development of efficient pathogen-targeted management strategies. The external and internal clinical signs of infection, histopathological alterations, and cytopathic effects on cell cultures caused by these viruses are similar. While CCV is more pathogenic to channel catfish fingerlings, BCAHV caused significant mortality in blue catfish. Younger catfish are more vulnerable to viral infections. Crowding of fish and increased viral loads significantly increased viral infectivity and associated mortalities. Development of disinfection protocols, vaccines, and establishment of new catfish cell lines will aid with the management of these viruses. Both in vitro and in vivo experiments indicated the inactivation of CCV in the presence of a commercial disinfectant (active ingredient potassium peroxymonosulfate). An attenuated CCV vaccine was developed by serial passage of the wildtype virus in catfish cell lines. This attenuated vaccine was administered to channel and hybrid catfish fingerlings via immersion. Thirty days post immunization, the immunized and non-immunized fish were exposed to wildtype CCV. Results indicated that the vaccine significantly improved the survival of immunized channel and hybrid catfish compared to the non-immunized group confirming the protective immunity conferred by the attenuated virus vaccine. Further studies are underway to evaluate the efficacy of the vaccine.