The piscine immune system is well developed and is normally quite efficient in protecting healthy free ranging fish from parasitic diseases. However, when fish are cultured in high numbers and are stressed by adverse environmental factors (e.g. heavy metal pollution, low dissolved oxygen, nutritional deficiencies, and/or overcrowding), parasites may have the advantage and the risk of disease outbreak increases in the fish population. We know very little about innate immunity against parasites. Hence it has not been considered a viable strategy to protect fish from diseases. The alternative pathway of complement activation is the protective mechanism in certain fish species against hemoflagellates (Cryptobia salmositica and Cryptobia catostomi). This mechanism also operates in some resistant individuals (in a susceptible fish species) against C. salmositica. Complement is also involved in innate parasiticidal activities against adult intestinal tapeworms (Acanthobothrium quadripartitum) and encysting larval stages of digeneans (Diplostomum spathaceum and Cryptocotyle lingua). It is suggested here that more studies be conducted to elucidate the mechanism(s) of innate immunity in nonsusceptible host species, and also to follow the heredity of parasite resistant factor(s) in individuals that belong to an otherwise susceptible host fish species.The innate nonspecific cytotoxicity of leukocytes of flounders, infected with the copepod, Phrixocephalus cincinnatus, was significantly depressed compared to those from uninfected flounders. The target cells for the leukocytes were murine cells; future studies should include parasites as target cells to determine the importance of the depression on disease resistance in copepod-infected fish.Fish that survive Amyloodinium ocellatum, C. salmositica, Cryptobia bullocki, Trypanosoma danilewskyi, Ichthyophthirius multifiliis, Myxidium lieberkuehni, a myxosporean parasite (PKX), and D. spathaceum infections are generally protected from disease when they are later exposed to the same parasite. Complement fixing antibodies and/or cell-mediated immunity are important in acquired immunity against C. salmositica, C. bullocki, T. danilewskyi, I. multifiliis, Diplostomum spathaceum, Cryptocotyle lingua, and Posthodiplostomum minimum. A live C. salmositica-vaccine has been developed. The vaccine has fewer polypeptide bands and a few of the remaining polypeptides are antigenically different from those in the virulent strain. It does not cause disease in fish but has remained protective. Fish are assumed to, or are known to, respond immunologically to numerous other parasitic infections. These include: Cryptocaryon irritans, Myxosoma cerebralis, Gyrodactylus bullatarudis, Dactylogyrus vastator, Neobenedenia melleni, Telogaster opisthorchis, Ligula intestinalis, Diphyllobothrium, Caryophyllaeus laticeps, Pomphorhynchus laevis, Anguillicola crassus, and Larnaea cyprinacea. However, the precise role of the immune system in these infections has yet to be determined.In general, there are little antibody and cell-mediated responses during early myxosporean infections because the parasite antigenically mimics host tissues. The proliferative type of inflammation is the principal defense when spores are formed, resulting in parasite encapsulation. Melanomacrophages ingest spores in tissue and transport them to kidneys, spleen, or liver where they are encapsulated and destroyed. Also, cestodes are thought to adsorb host antigens on their body surface to evade the host immune system. The extent and the mechanism of host tissue mimicry by parasites, presumably to avoid or reduce the host immune response, are both fascinating and in need of more careful study in the future.Not much is known about immunodepression due to parasitic diseases in fish. This is an important phenomenon because it generally increases the susceptibility and mortality of infected fish when they are exposed to another pathogen. Also, it will adversely affect vaccination programs carried out against other pathogens. Immunodepression has been found in C. salmositica, Glugea stephani, and PKX infections. It is suggested here that other parasitic infections should be closely examined for their effects on the piscine immune system. It is also beneficial to more closely evaluate the interactions of multiple infections (microbial and parasitic) and their effects on the fish.