Rotavirus-induced diarrhea is responsible for the death of approximately 800,000 children per year. Jennerian and modified Jennerian anti-rotavirus vaccines currently being tested have a moderate protective effect against rotavirus disease. Optimization of these vaccines, development of more efficient rationally designed vaccines, and identification of other strategies to prevent or treat rotavirus disease will rely on a thorough understanding of the host-virus relationship and especially on the immune mechanisms developed by the host against rotavirus. Recent advances in our understanding of the mouse model of rotavirus infection will enhance the understanding of human rotavirus disease.