Simple SummaryXenopus laevisis an anuran amphibian that has been used for decades as the principal vertebrate model to study embryonic development. Among the advantages of this species, one can mention its evolutionary closeness to higher vertebrates in terms of physiology, gene expression and organ development. In recent years, this model has gradually attracted the attention of ecotoxicologists, since it can be a good indicator of habitat diversity, biological variety and local stressors. In this review, we summarize the main available literature on the use ofX. laevisin different biological fields, highlighting its advantages and great versatility.AbstractIn vitro systems have been mainly promoted by authorities to sustain research by following the 3Rs principle, but continuously increasing amounts of evidence point out that in vivo experimentation is also of extreme relevance.Xenopus laevis, an anuran amphibian, is a significant model organism in the study of evolutionary developmental biology, toxicology, ethology, neurobiology, endocrinology, immunology and tumor biology; thanks to the recent development of genome editing, it has also acquired a relevant position in the field of genetics. For these reasons,X. laevisappears to be a powerful and alternative model to the zebrafish for environmental and biomedical studies. Its life cycle, as well as the possibility to obtain gametes from adults during the whole year and embryos by in vitro fertilization, allows experimental studies of several biological endpoints, such as gametogenesis, embryogenesis, larval growth, metamorphosis and, of course, the young and adult stages. Moreover, with respect to alternative invertebrate and even vertebrate animal models, theX. laevisgenome displays a higher degree of similarity with that of mammals. Here, we have reviewed the main available literature on the use ofX. laevisin the biosciences and, inspired by Feymann’s revised view, “Plenty of room for biology at the bottom”, suggest thatX. laevisis a very useful model for all possible studies.