Pythiosis is suspected to be heavily underdiagnosed due to unfamiliarity with the disease, the rapid progression and morbidity, and the difficulty in making a diagnosis. Symptoms often appear once the disease has progressed to the point where treatment are less effective.

As the organism is neither a bacterium, virus, nor fungus, routine tests often fail to diagnose it. In cytology and histology, the organism does not stain using Geisma, H&E, or Diff-Quick. GMS staining is required to identify the hyphae in slides. Additionally, the symptoms are usually nonspecific and the disease is not normally included in a differential diagnosis.

Biopsies of infected tissues are known to be difficult to culture, but can help narrow the diagnosis to several different organisms. A definite diagnosis is confirmed using ELISA testing of serum for pythiosis antibodies, or by PCR testing of infected tissues or cultures.

Due to the poor efficacy of single treatments, pythiosis infections are often treated using a variety of different treatments, all with varying success. Most successful treatments include surgery, immunotherapy, and chemotherapy.

Aggressive surgical resection is the treatment of choice for pythiosis. Because it provides the best opportunity for cure, complete excision of infected tissue should be pursued whenever possible. When cutaneous lesions are limited to a single distal extremity, amputation is often recommended. In animals with gastrointestinal pythiosis, segmental lesions should be resected with 5-cm margins whenever possible. Unfortunately, surgical excision of tissue and amputation do not guarantee complete success and lesions can reappear. So, surgery is often followed by other treatments.

An immunotherapy product derived from antigens of "P. insidiosum" has been used successfully to treat pythiosis.

Case reports indicate the use of the following chemotherapy treatments with varying success: potassium iodide, amphotericin B, terbinafine, itraconazole, fluconazole, ketoconazole, natamycin, posaconazole, voriconazole, prednisone, flucytosine, and liposomal nystatin.

In humans, it can cause arteritis, keratitis, and periorbital cellulitis. This has previously been thought to be a rare disease with only 28 cases reported in the literature up to 1996. However, keratitis due to Pythium may be more common than previously thought, accounting for a proportion of cases that were due to unidentified pathogens. Although this disease was first reported in 1884 the species infecting humans - "Pythium insidiosum" - was only formally recognised in 1987. Diagnosis can be difficult in part because of a lack of awareness of the disease. It does not appear to be transmissible either animal to animal or animal to human. There appear to be three clades of this organism: one in the Americas, a second from Asia and Australia and a third with isolates from Thailand and the USA. The most probable origin of the organism seems to be in Asia.

Most human cases have been reported in Thailand, although cases have been reported elsewhere. In humans, the four forms of the disease are: subcutaneous, disseminated, ocular, and vascular. The ocular form of the disease is the only one known to infect otherwise healthy humans, and has been associated with contact lens use while swimming in infected water. This is also the rarest form with most cases requiring enucleation of the eye. The other forms of the disease require a pre-existing medical condition, usually associated with thalassemic hemoglobinopathy. Prognosis is poor to guarded and treatments include aggressive surgical resection of infected tissue, with amputation suggested if the infection is limited to a distal limb followed by immunotherapy and chemotherapy. A recently published review lists nine cases of vascular pythiosis with five survivors receiving surgery with free margins and all except one requiring amputation. The same review lists nine cases of ocular pythiosis with five patients requiring enucnleation of the infected eye and four patients requiring a corneal transplant.

Treatment for phycomycosis is very difficult and includes surgery when possible. Postoperative recurrence is common. Antifungal drugs show only limited effect on the disease, but itraconazole and terbinafine hydrochloride are often used for two to three months following surgery. Humans with "Basidiobolus" infections have been treated with amphotericin B and potassium iodide. For pythiosis and lagenidiosis, a new drug targeting water moulds called caspofungin is available, but it is very expensive. Immunotherapy has been used successfully in humans and horses with pythiosis. Treatment for skin lesions is traditionally with potassium iodide, but itraconazole has also been used successfully.

Entomophthoramycosis (or Entomophthoromycosis) is a mycosis caused by Entomophthorales.

Examples include basidiobolomycosis and conidiobolomycosis.

Zygomycosis is the broadest term to refer to infections caused by "bread mold fungi" of the zygomycota phylum. However, because zygomycota has been identified as polyphyletic, and is not included in modern fungal classification systems, the diseases that zygomycosis can refer to are better called by their specific names: mucormycosis (after Mucorales), phycomycosis (after Phycomycetes) and basidiobolomycosis (after Basidiobolus). These rare yet serious and potentially life-threatening fungal infections usually affect the face or oropharyngeal (nose and mouth) cavity. Zygomycosis type infections are most often caused by common fungi found in soil and decaying vegetation. While most individuals are exposed to the fungi on a regular basis, those with immune disorders (immunocompromised) are more prone to fungal infection. These types of infections are also common after natural disasters, such as tornadoes or earthquakes, where people have open wounds that have become filled with soil or vegetative matter.

The condition may affect the gastrointestinal tract or the skin. In non-trauma cases, it usually begins in the nose and paranasal sinuses and is one of the most rapidly spreading fungal infections in humans. Common symptoms include thrombosis and tissue necrosis. Treatment consists of prompt and intensive antifungal drug therapy and surgery to remove the infected tissue. The prognosis varies vastly depending upon an individual patient's circumstances.

Pathogenic zygomycosis is caused by species in two orders: Mucorales or Entomophthorales, with the former causing far more disease than the latter. These diseases are known as "mucormycosis" and "entomophthoramycosis", respectively.

- Order Mucorales (mucormycosis)

- Family Mucoraceae

- "Absidia" ("Absidia corymbifera")

- "Apophysomyces" ("Apophysomyces elegans" and "Apophysomyces trapeziformis")

- "Mucor" ("Mucor indicus")

- "Rhizomucor" ("Rhizomucor pusillus")

- "Rhizopus" ("Rhizopus oryzae")

- Family Cunninghamellaceae

- "Cunninghamella" ("Cunninghamella bertholletiae")

- Family Thamnidiaceae

- "Cokeromyces" ("Cokeromyces recurvatus")

- Family Saksenaeaceae

- "Saksenaea" ("Saksenaea vasiformis")

- Family Syncephalastraceae

- "Syncephalastrum" ("Syncephalastrum racemosum")

- Order Entomophthorales (entomophthoramycosis)

- Family Basidiobolaceae

- "Basidiobolus" ("Basidiobolus ranarum")

- Family Ancylistaceae

- "Conidiobolus" ("Conidiobolus coronatus/Conidiobolus incongruus")