Cryptosporidium parvum is an important zoonotic protozoan pathogen that causes acute infection and self-limiting gastrointestinal disease in neonatal calves. There are currently no consistently effective antimicrobials available to control cryptosporidiosis. Therefore, immunotherapeutic and vaccination protocols offer the greatest potential for long-term control of the disease. In order to devise effective control measures, it is important to better define mucosal immunity to C. parvum in young calves. This review summarizes the information that has accumulated over the last decade which helps to define the intestinal mucosal immune system in neonatal calves, and the events that occur in the intestinal mucosa after infection by C. parvum.