Amebiasis, caused by the protozoan parasite Entamoeba histolytica, affects more than 50 million people worldwide, with over 100,000 deaths annually. The majority of cases are asymptomatic; however, significant morbidity and mortality are associated with illness in the remaining 10% of cases. Recent advances in the understanding of the mechanism of infection by E. histolytica, the role of the innate immune system, and the role of genetic disposition to infection will allow the development of novel detection and treatment methods. The disease mechanisms, clinical findings, therapeutic strategies, and important developments regarding amebiasis are discussed here.