Schistosomes are parasitic flatworms that cause schistosomiasis, a Neglected Tropical Disease affecting at least 249 million people worldwide. It is the most important waterborne disease in America introduced to this continent during the time of the African slave trade. Of the seven species that infect humans, only Schistosoma mansoni is present in America. Schistosomiasis is endemic in Brazil, Suriname, Venezuela, Dominican Republic, Guadeloupe, and St. Lucia. Around 1.8 million people in the region, mostly in Brazil, are thought to be infected, with 25 million living at risk of contracting the disease. The main risk factor for infection is skin exposure through household, work, or recreational activities in water bodies contaminated with cercariae, the infective larval stage of the parasite, released by freshwater mollusks of the genus Biomphalaria, that eventually enter the human skin. Adult worms in the porto-mesenteric venous system release hundreds of eggs which leave the body by stools or remain trapped in the intestine and liver, causing intestinal and hepatic pathology progressing to portal hypertension. Initially, schistosomiasis control was based on snail elimination with chemical moluscicides; since 1984 the strategy was reoriented to selective or mass chemotherapy and, since 2006, to preventive chemotherapy with praziquantel. Migration of rural populations, socioeconomic improvement, potable water supply, sanitation, increased exposure of flowing populations toward water bodies during weekends, invasion of exotic snails, chemotherapy program, and persistence of susceptible Biomphalaria species in endemic countries are factors that have modified the epidemiology in different ways in the six countries affected in America where prevalence varies.