Cryptosporidiosis, the leading cause of endemic and epidemic diarrheal disease worldwide, has been increasingly recognized within the immunosuppressed population of the United States since the AIDS epidemic began in 1982. Cryptosporidium parvum, the causative agent, is an intestinal, spore-forming protozoan that invades enterocytes, where it replicates to produce highly infectious and resistant oocysts. Transmission of these oocysts is by the fecal–oral route, and the incubation period is 2–14 days. Although healthy hosts may be asymptomatic or experience mild, self-limited symptoms, the immunocompromised host often presents with continuous, copious, watery diarrhea for an extended period. In such patients, infection with C. parvum may lead to dehydration, malabsorption, and nutritional deficiencies. C. parvum is usually confined to the gastrointestinal tract; however, depending on the degree of immunosuppression and strain of protozoan, extraintestinal infections can occur. The most common method of diagnosis is microscopic identification of the 4-μm to 6-μm oocysts in stool using a modified acid-fast staining technique. Direct immunofluoresence with monoclonal and polyclonal antibodies to the oocyst wall and a specific C. parvum enzyme–linked immunosorbent assay also are available; however, these tests most often are used in research settings and water treatment plants. To date, there is no effective cure or treatment for cryptosporidiosis. In healthy patients, antidiarrheal agents may provide temporary relief, whereas combination antibiotic therapy with paromomycin and azithromycin has been most effective in the immunosuppressed patient. Although treatment remains limited, new research that may prevent attachment and invasion of the parasite currently is being explored.