Natural susceptibility or resistance of fish towards various pathogens (viral, bacterial, parasitic, fungal) may involve a range of anatomical, physiological and immunological elements. The mere chemical composition and the anatomy of the external fish surfaces are likely to affect pathogen adherence and may prevent entrance of pathogens. Certain conformations of membrane proteins may act as an external shield and determine if a virus is able to attach to and infect a host cell. Innate and adaptive immune mechanisms are nonetheless always activated and play a central role when the pathogens reach the host mucosa in order to enter the organism. These traits are all inherited and thereby available for selection and selective breeding. Classical breeding programmes, aiming at increasing the natural resistance of fish towards various diseases, span over decades due to the long generation time of the fish. They have shown success in a number of systems, but due to the increasing amount of pathogens challenging aquacultured fish, the fish farm industry may benefit from improved and faster genetic breeding methods. The use of genome-wide association studies (GWAS), recording of markers such as microsatellites and single nucleotide polymorphisms (SNP), makes marker-selected breeding possible. Several studies have proven these methods are able to describe quantitative trait loci (QTL) and pinpoint individual fish with a high natural resistance towards diseases. Following experimental exposure of a fish population to a certain pathogen, the most susceptible fish will exhibit clinical symptoms whereafter they are immediately euthanized and DNA-typed. Surviving fish showing no disease signs will subsequently be sampled and correspondingly analysed. By comparing the SNP composition among surviving and dead fish, or by focusing on time to death upon exposure, the specific markers associated with genetic resistance are revealed and their localization in the host genome determined with high precision. This information can then be applied by selection of DNA-typed parent fish, whereby a new generation of fish with increased resistance can be produced within months. In addition, further analyses of the genomic regions with relevant markers and concomitant transcriptome analyses allow identification of immune genes (related to innate and/or adaptive responses) associated with disease resistance.