Sustainable health management in aquaculture is crucial due to fast expansion and intensification in this activity sector. In spite of the limited knowledge about intestinal microbiome in fish, empirical probiotic treatments have been increasingly tested on the basis of the applications that have been developed for human and land animals. Many new candidate probiotics have been isolated from fish gut, with antagonistic properties against specific pathogens, and other features potentially beneficial to fish health. There were also some attempts to introduce prebiotics and herb medicines in fish feeds. Some insight into translational research on host-microbes interactions may come from experimenting on fish as model, especially when gnotobiotic conditions can be maintained during the first larval stages, and when the association between microbes and the intestinal wall can be observed in vivo.