<p>Heterosis-based hybrid breeding mainly relies on robust systems of cytoplasmic male sterility (CMS) and its restoration by nuclear-encoded restorer-of-fertility (Rf) genes and Rf-like (RFL) genes. Most cloned Rf genes encode pentatricopeptide repeat (PPR) proteins that regulate mitochondrial RNA metabolism. More recently, mitochondrial transcription termination factor (mTERF) proteins have emerged as an additional class of fertility restorers, expanding the molecular basis of CMS Rf interactions beyond PPRs. This review synthesizes current knowledge on the genetic architecture and molecular mechanisms of fertility restoration in wheat and other cereals, with emphasis on the roles of four classes of genes, namely Rf, RFL, PPR and mTERF genes, which are not completely independent, since there is some overlap among Rf genes and PPR genes. We discuss the mechanistic basis of CMS, molecular modes of restoration, structural features of PPR proteins and their RNA recognition code, and the emerging significance of mTERF proteins. Special attention is given to wheat, including the mapping and functional characterization of major Rf loci such as Rf1, Rf3, Rf4, and Rf9. We highlight recent advances in genomics, transcriptomics, and gene editing that have accelerated the identification and functional validation of fertility restorer genes (using techniques like CRISPR/Cas gene editing). Finally, we discuss the implications of these findings for hybrid wheat breeding and outline future research directions focusing on nuclear mitochondrial interactions and molecular design of CMS Rf systems.</p>