<p>Functional feeds designed to enhance the host’s immune response and improve disease resistance are among the most popular strategies to mitigate the impact of infectious diseases and abiotic stressors in aquaculture. While reviewing the current scientific literature on this issue, we have detected that there is a need to standardize the evaluation criteria for feed additives with immunostimulant properties in terms of the duration of the trial and selection of key end-points related to the expected effect of the dietary intervention. The evaluation of the disease protective role of a feed additive should not be based only on end-points from cellular and immune biomarkers, but it should also be complemented with end-points based on survival data of specimens exposed to an <i>in vivo</i> infective challenge. We also recommend giving special consideration to the basal diet used in these studies since the inclusion of certain ingredients may have confounding results with those expected from the additive or functional ingredient of interest. Regardless of the in vivo challenge model selected (balneation, cohabitation, intraperitoneal injection, or oral/anal intubation), abiotic factors such as temperature, water flow, light, and water quality strongly influence the development of disease and must be&#xa0;also taken into consideration when designing experimental challenge models. Thus, it is of paramount importance to standardize the studies testing the efficacy of functional diets designed to protect the host from infectious agents and to assist in harmonizing the interpretation of their results.</p>