The aim of the work was to evaluate long-term results of studies focusing on improving methods for preventing and treating fish diseases using selected natural and syntetic immunomodulators and vaccines in fish culture. Simultaneously, attention is drawn to infectious or environmental threats against which appropriately composed immunoprophylaxis can be used in production cycles. Fish culture is intensifying in Poland and globally, which means that the role of prevention and well-designed prophylaxis is of increasing significance to the prevention and treatment of fish diseases. Currently, 33 fish species are cultured in Poland as stocking material or for production. The primary methods for preventing diseases in controlled fish culture are ensuring the welfare of fish and other prophylactic methods, including immunoprophylaxis. Many infectious and non-infectious threats that can cause direct losses and limit fish culture are present in the aquatic environment. Fish diseases generally stem from the simultaneous action of many factors that coincide and are difficult to distinguish. Pesticides (organochlorine insecticides, organophosphorus herbicides), aromatic hydrocarbons, pentachlorophenol, heavy metals, and chemotherapeutics are particularly toxic to fish. Biodegradation, which is continual in aquatic environments, is a process by which toxic and other substances that negatively affect fish become bioavailable and impact the immune system, the functioning of which is a specific bioindicator of environmental quality. Innate immunity plays a key role in the defense against disadvantageous factors, which also include pathogens. Immunomodulation methods can protect resistance mechanisms, thereby increasing disease prevention and treatment in controlled fish culture.