In the Mekong River basin, the first case of schistosomiasis was reported in 1957. In the 1960s, endemic areas of the infection, of which profiles were similar to those of schistosomiasis japonica, were discovered in Khong Island, Laos, to Kratie province, Cambodia. A new intermediate snail host; Neotricula aperta was identified and the Mekong strain of schistosome was elevated to a new species: Schistosoma mekongi in 1978. Baseline epidemiological surveillance was performed and schistosomiasis mekongi was described as a public health implication in the middle Mekong River basin. Because of political and economical confusion, endemic situation had become worse, and no control program had been implemented until mass treatment program with praziquantel on Khong Island in 1983. Since then, the prevalence of S. mekongi infection has rapidly decreased in each endemic area. Serological diagnosis has been useful to detect new but low endemic foci. Clinical manifestations of S. mekongi infection are similar to those of S. mansoni and S. japonicum infections. As the reduction of prevalence and intensity of S. mekongi infection, morbidity due to the disease has changed, and ultrasonographic examination is now useful to evaluate morbidity due to schistosomiasis mekongi. Transmission of the disease occurs in a couple of months during low water season. Control of N. aperta is difficult and long-lasting effective control measurements have, so far, not been available. In the next step for controling S. mekongi infection, mass treatment should be continued, and it is needed to combine other appropriate control activities.