Garra rufa, commonly known as the "doctor fish", is a freshwater cyprinid native to warm regions of the Middle East. Since the late twentieth century, it has been widely utilized in spas for alternative therapeutics and fish pedicures (or manicures) for dermatological diseases such as psoriasis and eczema. Owing to its unique characteristics, there is growing interest in exploring various applications of G. rufa. This review provides a comprehensive summary of the phylogenetic position, ecology, biological characteristics, and breeding methods of G. rufa, and provides insights into its use as a therapeutic fish. Notably, the ability of G. rufa to thrive in high-temperature environments exceeding 37 °C distinguishes it from other cyprinids and suggests its potential as a model for human diseases, such as human infectious diseases, and in use in cancer xenograft models for high-throughput drug screening. The ongoing genome sequencing project for G. rufa aims to elucidate the mechanisms underlying its high-temperature tolerance and offers valuable genomic resources. These efforts have resulted in significant advances in fish aquaculture, species conservation, and biomedical research. rufa is a benthic fish that prefers shallow, fast-moving, warm waters with rocky or sandy bottoms conducive to its feeding habits. The native environments of different Garra species differ in several ways. For example, G. rufa is dominant in turbid, large, and relatively deep streams, whereas G. rezai is dominant in clear, shallow, and small streams. In the Tigris–Euphrates River, which is the natural habitat To date, few studies have been conducted on G. rufa culture, and the optimal conditions for its cultivation are gradually being defined [ 31 , 41 ]. The fertilized eggs of G. rufa are non-adhesive, sink to the bottom of the tank, and must be promptly relocated to prevent the parent fish from eating them. The eggs can be sterilized prior to incubation by immersion in 5 mg/L methylene blue for 40–60 min. The spawning frequency of G. rufa is once every 15–30 days, with 57–314 eggs produced with an average diameter of 2.83 mm. Pathogens introduced from the natural environment into aquaculture facilities can cause mortality, growth retardation, and decreased feed conversion rates in cultured fish, making proper quarantine essential. In G. rufa aquaculture, the use of sedative and anesthetic substances such as clove oil and 2-phenoxyethanol is recommended to reduce stress during transportation, parasite inspection, and other critical routine farming operations [ 46 , 47 ]. Conventional roles of G. rufa in human society G. rufa as “doctor fish” G. rufa , which has gained international recognition as the “doctor fish,” makes a unique contribution to the treatment of skin disorders, particularly psoriasis. This natural exfoliation process, often referred to as “ichthyotherapy,” involves patients immersing affected areas of their skin in water basins containing G. rufa (Fig. 2 e). The fish then feed on the dead skin, providing a therapeutic benefit. The use of the “doctor fish” as a complementary treatment for skin conditions is based on the ability of the fish to exfoliate, potentially improving the overall health of the skin. Patients with psoriasis, a chronic autoimmune skin condition characterized by red, flaky, and crusty patches of skin covered with silvery scales, have reported significant relief and reduction in symptoms following treatment with G. rufa [ 2 , 48 , 49 ]. The sanitary conditions of the water and the health status of the fish are critical for ensuring the safety and efficacy of treatment, including the use of certain water disinfectants [ 55 ]. Despite these concerns, the use of G. rufa in the treatment of skin diseases remains a topic of interest for dermatologists and patients seeking alternative or complementary therapies. As research advances, a clearer understanding of the benefits, limitations, and best practices associated with ichthyotherapy may emerge, potentially solidifying its application in the broader context of dermatological treatment. G . rufa may become an important alternative food source for humans in the near future, as global warming progresses [ 65 ]. Emerging roles of G. rufa in human health care and medical research Expansion of medical use as “doctor fish” The medical and therapeutic applications of G. rufa , particularly in dermatology and alternative medicine, have broadened considerably. In addition to its well-documented use in the treatment of psoriasis, G. rufa is used to assist in the management of eczema and various dry skin conditions. The removal of dead skin layers potentially reduces discomfort and improves the efficacy of moisturizing treatments. The potential of G. This attribute may extend its medical applications beyond conventional dermatology. In addition, G. rufa treatment is associated with stress relief and benefits to mental well-being. The unique sensation of fish nibbling is often described as gentle tickling, which induces relaxation and enhances the overall spa experience. A clinical trial of ichthyotherapy for psoriasis at Kangal Hot Springs in Türkiye reported a reduction in patient stress and enhancement in psychological well-being [ 4 ]. This suggests that the therapy could be applicable not only to dermatological diseases but also to various stress-related illnesses and mental disorders. However, similar to their rodent counterparts, small fish models have certain limitations. In particular, the requirements of different optimal growth temperatures are often overlooked. Fish are ectothermic, which means that the concept of internally regulated body temperature does not apply to them in its strictest sense. Nevertheless, temperatures higher than normal have been reported to profoundly influence the function of many organs, cause damage to the liver [ 79 – 81 ] and adipose tissues [ 82 ] and enhance the immune response [ 83 , 84 ].