Publisher Summary This chapter describes the immunological aspects of fish health. Fish live closely with their aquatic environment and living epidermal cell membranes have direct contact with all materials carried by water. Wild fish are exposed to many chemicals in their environment that may possess immunomodulatory potential. Some of these substances affecting fish health are from natural sources, such as low pH in some lakes resulting from the accumulation of tannic acid from forest degradation. In vitro assays describing the immunosuppressive effects of copper on the antibody-producing cells in isolated rainbow trout spleen cells shows the direct effect on the humoral immune response. In the assays, Spleen fragments were incubated in tissue culture media for 14 days after being injected with Yersinia ruckeri bacterins. The higher concentrations of copper in the media inhibited the formation of the antibody-producing cells. It is observed that tributyltin, an important antifouling agent used in exterior paints for boats, has immunosuppressive properties on the chemiluminescence response of macrophages in the toadfish.