Vaccination is an important disease management strategy used to maintain human and animal health worldwide. Vaccines developed for aquaculture have reduced antibiotic use in fish production. Original fish vaccines were bacterins (formalin-killed bacteria) delivered through immersion or injection that induced humoral (antibody) immunity. Next generation vaccines relied on multiple killed antigens delivered with an adjuvant to enhance vaccine effectiveness. Work in the 1990s showed the use of various strategies to develop modified live vaccines for use in fish. A modified live vaccine is a live pathogen that has been rendered non-pathogenic or avirulent by physical, chemical, or genetic engineering methods. The modified live vaccine typically retains its ability to infect the host which allows for effective presentation of protective antigens to generate cellular immunity (CD4 or CD8 T-cell responses). Modified live vaccines are advantageous in that they can be easily delivered (i.e., by immersion to young fish) and stimulate both humoral and cellular immunity of long duration. Disadvantages include issues with modified live vaccine safety to the host and environment. A successful modified live vaccine for use in warm water aquaculture is used to highlight the live vaccine strategy.