Natural populations v. inbred stocks provide a much richer resource for identifying the effects of nucleotide substitutions because natural populations have greater polymorphism. Additionally, natural populations offer an advantage over most common research organisms because they are subject to natural selection, and analyses of these adaptations can be used to identify biologically important changes. Among fishes, these analyses are enhanced by having a wide diversity of species (>28 000 species, more than any other group of vertebrates) living in a huge range of environments (from below freezing to > 46° C, in fresh water to salinities >40 ppt.). Moreover, fishes exhibit many different life-history and reproductive strategies and have many different phenotypes and social structures. Although fishes provide numerous advantages over other vertebrate models, there is still a dearth of available genomic tools for fishes. Fishes make up approximately half of all known vertebrate species, yet <0·2% of fish species have significant genomic resources. Nonetheless, genomic approaches with fishes have provided some of the first measures of individual variation in gene expression and insights into environmental and ecological adaptations. Thus, genomic approaches with natural fish populations have the potential to revolutionize fundamental studies of diverse fish species that offer myriad ecological and evolutionary questions.