Knowledge of jawed fish immune systems obtained in the last 15 years has been mostly obtained through the sequencing of genomes of different fish species and from the use of high-throughput techniques such as transcriptomic analysis and RNA sequencing, which has allowed characterization of immune gene responses at the transcriptomic level. Although these have been important tools for exploring the complexities of the immune responses of fish species, the next generation of knowledge requires the use of new tools and methods capable of unveiling the diversity of immune cells and molecules in jawed fish, the network of interactions and responses, and the mechanisms leading to immune protection against pathogens. For more than 10 years, many laboratories have been engaged in developing antibodies against key molecules of jawed fish immune systems in several different species because the lack of sequence conservation of most immune genes makes it impossible to use the large panel of antibodies against mammalian molecules for recognition of fish molecules. The numerous genes encoding cytokines and receptors have now been used to make recombinant proteins available, allowing studies of the complex network of cytokine and receptor functions central to fish immune responses. From many laboratories, new and interesting knowledge about immune cells, their functions and interactions can be studied with the availability of new tools and methods have begun to provide a clear understanding fish immunity at the protein and cellular levels. This Research Topic gives a comprehensive overview of the current knowledge of jawed fish immune responses with a particular emphasis on structural and functional studies at the protein and cellular levels.