Pythiosis is an invasive, ulcerative, pyogranulomatous disease caused by Pythium insidiosum, a fungus-like oomycete that has been reported to affect humans, horses, dogs, and other mammals mainly in tropical and subtropical areas of the world. The disease is characterized by an eosinophilic granulomatous and a Th2 immune response which in turn helps to protect the fungus from the host cells. Pythiosis can present clinically in subcutaneous, gastrointestinal, and vascular tissues or in a systemically disseminated form depending on the species and site of infection. Changes in iron metabolism and anemia are commonly observed. The diagnosis is accomplished through clinical and pathological features, laboratory characteristics of cultures, serological and molecular tests. Treatment includes radical surgery, antimicrobial drugs, immunotherapy or a combination of these treatments. Immunotherapy is a practical and non-invasive alternative for treating pythiosis which is believed to promote a switch from a Th2 to Th1 immune response, resulting in a favorableclinical response. This therapy has demonstrated cure rates above 70% and 55% in horses and humans but low cure rates in dogs and cats. Despite the curative properties of this type of immunotherapy, the antibodies that are produced do not prevent host reinfection. Thus, development of effective adjuvants and new diagnostic techniques for early disease diagnosis are of utmost importance. The aim of this review was to promote pythiosis awareness and to provide an update about the immunotherapy and immunobiology of this disease. Pythiosis is an invasive, ulcerative, pyogranulomatous disease caused by Pythium insidiosum, a fungus-like oomycete that has been reported to affect humans, horses, dogs, and other mammals mainly in tropical and subtropical areas of the world. The disease is characterized by an eosinophilic granulomatous and a Th2 immune response which in turn helps to protect the fungus from the host cells. gastro in, and vascular tissues or in a systemically disseminated form depending on the species and site of infection. Changes in iron metabolism and anemia are commonly observed. The diagnosis is accomplished through clinical and pathological features, laboratory characteristics of cultures, serological and molecular tests. Treatment includes radical surgery, antimicrobial drugs, immunotherapy or a combination of these treatments. invasive alternative for treating pythiosis which is believed to promote a This therapy has been cure rates above 70% and 55% in horses and humans but low cure rates in dogs and cats. Despite the curative properties of this type of immunotherapy, the antibodies that are done do not prevent host reinfection. Thus, development of effective adjuvants and new diagnostic techniques for early disease diagnosis are of utmost importance. The aim of this review was to promote pythiosis awareness and to provide an update about the immunotherapy and immunobiology of this disease.