Biofortification is the process of improving the bioavailability of essential nutrients in food crops either through conventional breeding or modern biotechnology techniques. Rice is one of the most demanding staple foods worldwide. Most global population live on a diet based on rice as the main carbohydrate source that serve as suitable target for biofortification. In general, polished grain or white rice contains nutritionally insufficient concentration of iron (Fe) to meet the daily requirements in diets. Therefore, iron biofortification in rice offers an inexpensive and sustainable solution to mitigate iron deficiency. However, understanding on the mechanism and genes involved in iron uptake in rice is a prerequisite for successful iron biofortification. In this chapter, the overview of iron uptake strategies in plants and as well as different iron-biofortified approaches used in rice will be outlined. Then, the challenges and future prospects of rice iron biofortification to improve global human health will also be discussed.