Hybrid sterility is the most common form of postzygotic reproductive isolation in plants. The best-known example is perhaps the hybrid sterility between indica and japonica subspecies of Asian cultivated rice (Oryza sativa L.). Major progress has been reported recently in rice in identifying and cloning hybrid sterility genes at two loci regulating female and male fertility, respectively. Genetic analyses and molecular characterization of these genes, together with the results from other model organisms especially Drosophila, have advanced the understanding of the processes underlying reproductive isolation and speciation. These findings also have significant implications for crop genetic improvement, by providing the feasibility and strategies for overcoming intersubspecific hybrid sterility thus allowing the development of intersubspecific hybrids.