Technical Abstract: Ichthyophthiriasis causes high mortalities of fish and leads to heavy economic loss in aquaculture. The disease is caused by a ciliated protozoan Ichthyophthirius multifiliis Fouquet (Ich) that is a major parasitic disease of freshwater fish worldwide. This study determined mechanisms of disease caused by Ich, compared prevention and treatment, and evaluated immune response and vaccination. It is difficult to control the parasite using chemical treatment since the parasite penetrates into fish skin and gills, is costly for fish farmers, and there is concern for food and environmental safety. Channel catfish immunized with live theronts or sonicated trophonts acquired protection against Ich. The immunized fish showed higher levels of anti-Ich antibodies in the skin and serum than non-immunized fish. Parasite infection and mortality did not occur in fish immunized with live theronts. Fish immunized with sonicated trophonts had a low infection and mortality compared to non-immunized fish. The results of this study show that vaccination against Ich is an alternative to chemical treatments since the surviving fish from an Ich infection develop immunity against reinfection by the parasite.