Immunity to Cryptosporidium involves both innate and adaptive immune responses. Initially, chemokines such as CXCL-10 and perhaps CXCL-8 attract effector cells to the site of infection. Activation of an early immune response by IL-15 is critical for initial clearance of the parasite. CD4+ T cells and IFN-γ play key roles in the human memory response. The function of B cells and CD8+ T cells requires further research. The intestinal inflammatory response seems to mediate diarrhea. Substance P is likely a key mediator of gastrointestinal symptoms in human infection; prostaglandins have been implicated in animal models, but their role in human infection is unclear. TGF-β and IL-10 are likely involved in anti-inflammatory and healing processes. They may also lead to generation of secretory IgA, which may prevent reinfection. Despite the difficulties of investigating human intestinal immune responses, such studies provide important insights into the human mucosal immune response. Since cryptosporidiosis has a significant impact on the health of immunocompromised patients and children in developing countries, further study of the pathogenesis and host immune response in patients with cryptosporidiosis is warranted. Cryptosporidium infection may also provide an important model for dissecting the human intestinal mucosal immune response towards other pathogens and for studying aberrant responses in inflammatory bowel disease. Copyright © 2008, American Society for Microbiology. All Rights Reserved.