The small teleost fish Astyanax mexicanus has emerged as an outstanding model for studying many biological topics in the context of evolution. A major attribute is conspecific surface dwelling (surface fish) and blind cave dwelling (cavefish) morphs that can be raised in the laboratory and spawn large numbers of transparent and synchronously developing embryos. More than 30 cavefish populations have been discovered, mostly in northeastern Mexico, and some are thought to have evolved independently from surface fish ancestors, providing excellent models of parallel and convergent evolution. Cavefish have evolved eye and pigmentation regression, as well as modifications in brain morphology, behaviors, heart regenerative capacity, metabolic processes, and craniofacial organization. Thus, the Astyanax model provides researchers with natural “mutants” to study life in the challenging cave environment. The application of powerful genetic approaches based on hybridization between the two morphs and between the different cavefish populations are key advantages for deciphering the developmental and genetic mechanisms regulating trait evolution. QTL analysis has revealed the genetic architectures of gained and lost traits. In addition, some cavefish traits resemble human diseases, offering novel models for biomedical research. Astyanax research is supported by genome assemblies, transcriptomes, tissue and organ transplantation, gene manipulation and editing, and stable transgenesis, and benefits from a welcoming and interactive research community that conducts integrated community projects and sponsors the International Astyanax Meeting (AIM).