Abstract Heterosis or hybrid vigor is a phenomenon in which a hybrid progeny exhibits superior performance compared to their parental inbred lines. F1 hybrid seed production system is used for many crops and vegetables because of the high yield due to hybrid vigor. It has been over 100 years since the discovery of the hybrid vigor phenomenon; however, the molecular mechanism of hybrid vigor is still a mystery. Understanding the mechanism of hybrid vigor will allow developing more efficient breeding systems and contribute to food security. At this time, hybrid vigor research has mainly used genetic approaches providing a number of findings in many plant species. High throughput sequencing will make genetic analysis more efficient, and large-scale quantitative trait analysis or genome wide association analysis has been performed in some plant species. However recent works have revealed that epigenetic regulations also contribute to hybrid vigor. In this chapter, we will discuss the most recent findings suggesting that epigenetic regulation may play important roles in hybrid vigor.