Fish above the level of the agnatha display typical vertebrate adaptive immune responses characterized by immunoglobulins, T-cell receptors, cytokines, and major histocompatibility complex molecules. However, while the immune system of fish is quite different in its efficiency and complexity from that of higher vertebrates, our knowledge is sufficiently limited that we do not yet have a full understanding of the reasons for this difference. Filling the substantial gaps in our knowledge of the adaptive immune responses of fish will improve our understanding of their response to vaccines, and aid in the rational design of vaccines and protocols for vaccination.