Fish and other aquatic animals are subject to a broad variety of stressors because their homeostatic mechanisms are highly dependent on prevailing conditions in their immediate surroundings. Yet few studies have addressed stress as a potential confounding factor for bioassays that use fish as test subjects. Common stressors encountered by captive fish include physical and mental trauma associated with capture, transport, handling, and crowding; malnutrition; variations in water temperature, oxygen, and salinity; and peripheral effects of contaminant exposure or infectious disease. Some stress responses are detectable through gross or microscopic examination of various organs or tissues; as reported in the literature, stress responses are most consistently observed in the gills, liver, skin, and components of the urogenital tract. In addition to presenting examples of various stressors and corresponding morphologic effects, this review highlights certain challenges of evaluating stress in fish: (1) stress is an amorphous term that does not have a consistently applied definition; (2) procedures used to determine or measure stress can be inherently stressful; (3) interactions between stressors and stress responses are highly complex; and (4) morphologically, stress responses are often difficult to distinguish from tissue damage or compensatory adaptations induced specifically by the stressor. Further investigations are necessary to more precisely define the role of stress in the interpretation of fish research results.