Abstract Fish, first jawed vertebrate group appearing in evolution, have immune system similar to those of mammals. These early animals' innate and adaptive immune systems are completely developed, having head kidney and thymus as primary, spleen and mucosa associated lymphoid tissue as secondary immune organs. The adaptive immunity performs key role in defence against recurring infections and elimination of fish pathogens with the help of its memory cells, T‐cell‐receptors and immunoglobulins. Epidermal secretions including antibacterial peptides, lysozymes, lectins, complement and C‐reactive proteins which function in disruption of antigens, phagocytosis, inflammatory response and mending of tissue injury play a significant role as elements of fish immune system. Fish, however, have greater innate immunity than humans do. Estrogens play crucial role in immunomodulation through nuclear oestrogen receptors, which are found in majority of immune cells and lymphoid organs in fish. There is mounting proof that xenoestrogens, that can attach as agonists to oestrogen receptors, pose significant ecotoxicological risk by disrupting the defence mechanism in fish. Though less potent than natural oestrogen, they can bioaccumulate to finally reach a substantial dose. This review's objective is to give an overview of the fish defence system, its estrogenic regulation and estrogenic‐endocrine disruption.