Cystoisospora belli is a coccidian parasite of humans, with a direct fecal–oral transmission cycle. It is globally distributed, but mainly found in tropical and subtropical areas. Many cases of C. belli infections have been reported in patients with HIV, and in patients undergoing immunosuppressive therapy for organ transplants or those treated for tumours worldwide. Unsporulated or partially sporulated oocysts of C. belli are excreted in feces. When sporulated oocysts in contaminated water or food are ingested, asexual and sexual stages of C. belli are confined to the epithelium of intestines, bile ducts and gallbladder. Monozoic tissue cysts are present in extra-intestinal organs (lamina propria of the small and large intestine, lymph nodes, spleen, and liver) of immunosuppressed humans. However, a paratenic host has not been demonstrated. Cystoisospora belli infections can be persistent, lasting for months, and relapses are common; the mechanism of relapse is unknown. Recently, the endogenous stages of C. belli were re-examined and attention was drawn to cases of misidentification of non-protozoal structures in the gallbladder of patients as C. belli. Here, we review all aspects of the biology of C. belli, including morphology, endogenous stages, prevalence, epidemiology, symptoms, diagnosis and control.