Amebiasis, a parasitic disease transmitted by the unicellular protozoan parasite Entamoeba histolytica, is the cause of at least 100,000 deaths each year. The disease is mostly prevalent in developing countries and is one of the three common causes of death from parasitic diseases. The parasite has two stages in its life cycle in the host: the infective cyst and the invasive trophozoite. In the large intestine, the parasite feeds on bacteria and on cellular debris. No vaccine against amebiasis currently exists. Although metronidazole is the drug of choice for treating amebiasis, adverse effects in patients and potential resistance to metronidazole in other protozoa exist. About nine out of 10 people who are infected with E. histolytica are asymptomatic and in those individuals who develop symptoms, bloody diarrhea (amebic colitis) and liver abscess are the most common symptoms. One possible explanation for this observation is the difference in the gut microbiota between individuals that may significantly influence the host’s immune response in amebiasis and E. histolytica's virulence. Amebiasis is characterized by acute inflammation of the intestine with release of pro-inflammatory cytokines, reactive oxygen species and reactive nitrogen species from activated cells of the host's immune system. In recent years, significant advances on the cell biology of Entamoeba infection have been achieved through the development of new genetic tools to manipulate gene expression in the parasite and through the application of Omics tools. In this Research Topic, we welcome high quality original research articles, as well as review, opinion or method articles, on amebiasis including but not limited to the regulation of gene expression, cell biology and signaling, adaptation and resistance to environmental stresses, metabolism, pathogenesis and immunity, pathogenesis and microbiome, drug discovery and drug resistance.