This is a review article telling a 50-years old story about the studies on selenium deficiency and Keshan disease in China, an endemic heart disease with high case-fatality, as an example of translational research. Extensive cross-sectional epidemiological studies showed that low selenium concentrations in cereal grains and low selenium status of local residents were associated with the occurrence of Keshan disease. Several large population based intervention trials using oral administration of sodium selenite tablets showed significant reduction of Keshan disease incidence. Based on the above evidence, it was concluded that selenium deficiency is the major cause of Keshan disease, although other etiological factors could not be ruled out. The implications of the findings include: provided critical scientific evidence for selenium being an essential trace element for humans; as scientific basis for identifying minimum requirement and RDA/RNI for selenium; and as solid reference for the formulation of effective preventive measures for Keshan disease in China.