Opisthorchiasis in the Lower Mekong Subregion is a parasitic disease caused by the liver fluke Opisthorchis viverrini. This parasite has a well-documented distribution in Thailand, Lao PDR, Cambodia, Myanmar and Southern Vietnam. In this chapter, we describe the current knowledge of the epidemiology of O. viverrini infection, highlighting advances in control efforts made in the last four decades in Thailand and identifying ongoing gaps in our epidemiological knowledge which need to be filled to support efforts to permanently overcome the heavy morbidity and mortality burden caused by these parasites within their endemic regions.