In higher plants, pollen carries the male gametes. Male sterility, in which a plant generates abnormal anthers or aborted (inviable) pollen but normal embryo sacs, enables out-crossing to produce hybrids for the utilization of heterosis in agriculture. However, hybrid sterility also hinders crop breeding; for example, interspecific and intersubspecific hybrids always show various forms of sterility. This reproductive isolation prevents the production of hybrids with increased grain yields in key crops such as rice (Oryza sativa). In this chapter, we summarize the current understanding of the genetic and molecular bases of cytoplasmic male sterility, fertility restoration, and environment-sensitive genic male sterility in rice model systems. We also discuss how studies of these systems have shed light on cytoplasmic–nuclear interactions and plant–environment interactions. In addition, we also present new advances in understanding the molecular mechanisms of major loci for hybrid sterility in rice and highlight new strategies for overcoming reproductive barriers to better utilize heterosis in interspecific and intersubspecific hybrid rice.