The world population is increasing at an alarming rate, and there is a continued need to increase crop productivity to meet the food requirements. To meet the ever-increasing demand for food, cytoplasmic male-sterility (CMS) has been successfully exploited to develop hybrids for increasing crop production worldwide. However, large-scale cultivation of crop hybrids based on a single source of CMS may pose a serious challenge to sustainable crop production because of decreasing genetic diversity. This review analyses the potential for exploitation of different CMS systems for hybrid production, effects of CMS on various agronomic traits, and expression of resistance to insect pests and diseases in high-yielding hybrids of sorghum, maize, pearl millet, rice, wheat, and barley. Considerable information has been generated on the effects of CMS on physiology, yield, and agronomic characteristics of the plant. However, there is limited information on the effects of CMS on expression of resistance to insect pests and diseases. The available information indicates that the CMS lines are more susceptible to insect pests and diseases, and large-scale cultivation of hybrids based on a single source of CMS might result in pest outbreaks because of narrow genetic base. Therefore, there is a continuing need to evaluate various CMS systems in different genetic backgrounds for their effects on cultivar susceptibility to insect pests and diseases to develop strategies for large-scale deployment of pest-resistant hybrids on farmer's fields. Genetically engineered insect-resistant CMS lines can also be exploited to diversify the hybrid parents for sustainable crop production.