The stressful conditions associated with intensive fish farming increase the fish’s susceptibility to infectious diseases. Rising water temperatures due to climate change are also likely to see increased disease outbreaks and the emergence of new pathogens within farming systems. Disease outbreaks result in substantial economic losses to the aquaculture industry globally, in the region of several billion US dollars annually. Antibiotics are commonly used to control bacterial disease outbreaks. Antimicrobial resistance (AMR) has emerged as a global threat to human and animal health. In aquaculture, AMR poses significant challenges due to the widespread use of antimicrobial agents to prevent and treat diseases. There are increasing concerns about their impact on the environment, the development of antimicrobial resistance, and the risk of antibiotic residues in fish products. Vaccination has been shown to be effective in controlling infectious disease outbreaks and is routinely used for some fish species, especially for higher-value species such as Atlantic salmon. Vaccine use has been shown to reduce the use of antibiotics in fish farming. The main advantage of vaccines is that they are used prophylactically to prevent disease outbreaks from occurring, thus removing the need to use antibiotics. However, there is a lack of vaccines for many pathogens, and where vaccines are available, their uptake can be poor for some fish species, e.g. tilapia. Most commercial vaccines are based on killed whole-cell preparations administered to fish by intraperitoneal injection. These can be expensive and logistically difficult to administer in some countries, so farmers prefer to treat disease outbreaks with antibiotics rather than investing in disease prevention. This chapter provides an overview of the applications and benefits of vaccination, explores various vaccine types and their applications, and evaluates the impact of vaccination on AMR control.