Combustion of coal in thermal power plants generates huge quantities of coal fly ash (CFA) worldwide. CFA contains a series of plant-essential elements, and one distinct beneficial reuse option of CFA is its utilization as a soil amendment. Applying CFA to soil at appropriate rates can improve soil physicochemical properties, thereby enhancing plant growth and crop yields. Most CFAs are richer in selenium (Se) than non-seleniferous soils; using Se-rich CFA for soil amendment can increase the bioavalabily of Se in soil and enhance Se uptake by plants. Plant material rich in Se produced on CFA-amended soils can be blended with low-Se material in a diet or used as dietary supplementation to provide sufficient Se for those humans suffering Se-deficiency. Therefore, it is promising to use CFA as a soil amendment for Se biofortification to address the Se-deficiency issue in vast numbers of people worldwide. In this chapter, we survey and describe the concentration and speciation of Se in CFA, summarize factors affecting Se mobility and bioavailability in CFA-amended soils, and plant uptake of Se from CFA-amended soils, and assess the effects of CFA application on Se accumulation by plants, plant growth and crop yield. We also list and discuss the disadvantages, potential negative effects and hazards associated with the application of CFA in agriculture, and propose a few measures for efficient use of CFA for Se biofortification and hazard reduction and prevention.