Food-borne trematode infections, caused by liver flukes (Clonorchis, Fasciola, Opisthorchis), lung flukes (Paragonimus) and intestinal flukes (Echinostoma, Fasciolopsis, heterophyids), are significant public health problems, most notably in Southeast Asia and the Western Pacific. Globally, it is estimated that > 40 million people are infected among the 750 million people who live in endemic areas. The epidemiology of food-borne trematodiasis has changed over the past few decades, and now presents a dual picture. On the one hand, increasing numbers of infections are reported from non-endemic areas, and endemic areas are expanding due to larger areas utilised for aquaculture, domestic migration, declining socioeconomic conditions, lack of improved sanitation, and increasing availability of aquatic foods through wider distribution networks often without proper food inspections. On the other hand, social and economic advances in many Asian countries, going hand-in-hand with urbanisation, use of chemical fertilisers and, above all, the administration of safe, efficacious and inexpensive drugs, have significantly reduced the prevalence of food-borne trematode infections. In this review, the taxonomy, life cycle, and geographical distribution of the major food-borne trematodes, including issues of diagnosis and clinical disease manifestations, is summarised. The discovery, chemistry, pharmacological properties, safety, therapeutic efficacy and adverse effects of the current drugs of choice, namely praziquantel and triclabendazole, is then discussed. Recent advances on other drugs and contemporary investigations on novel compounds that might become important players in chemotherapy are highlighted. Finally, the need for research and development of new trematocidal drugs that - employed in concert with health education, improved sanitation and enhanced food safety - are key factors for sustainable control of food-borne trematodiasis, is highlighted.