Orthologs and paralogs are two types of homologous genes that evolved through vertical descent from a single ancestral gene (orthologs) and duplication (paralogs), respectively. These concepts are crucial in evolutionary genomics for constructing robust gene classifications and functional annotations. Orthologous relationships can be established for most genes across taxonomically distant species, and their identification is vital for understanding evolutionary trends and functional implications. The definitions and subtypes of orthologs and paralogs, along with methods for their identification, are discussed. Orthologs and paralogs are entangled in complex relationships due to events like gene loss, horizontal gene transfer (HGT), and gene rearrangements. Correct usage of these terms is essential for clarity in genome evolution descriptions. The review explores the evolutionary and functional implications of these concepts, including the roles of gene duplication, HGT, and gene fusion/fission. It also addresses the challenges in distinguishing orthologs from paralogs and the impact of lineage-specific gene loss and HGT on orthology and paralogy. The review highlights the importance of orthology in evolutionary genomics and the need for accurate identification methods, such as phylogenetic analysis and sequence similarity approaches, to disentangle orthologous and paralogous relationships. The discussion covers the complexities of orthologous clusters, the molecular clock hypothesis, and the emergence of xenologs, pseudoorthologs, and pseudoparalogs. The review emphasizes the significance of these concepts in understanding gene evolution and functional diversification.Orthologs and paralogs are two types of homologous genes that evolved through vertical descent from a single ancestral gene (orthologs) and duplication (paralogs), respectively. These concepts are crucial in evolutionary genomics for constructing robust gene classifications and functional annotations. Orthologous relationships can be established for most genes across taxonomically distant species, and their identification is vital for understanding evolutionary trends and functional implications. The definitions and subtypes of orthologs and paralogs, along with methods for their identification, are discussed. Orthologs and paralogs are entangled in complex relationships due to events like gene loss, horizontal gene transfer (HGT), and gene rearrangements. Correct usage of these terms is essential for clarity in genome evolution descriptions. The review explores the evolutionary and functional implications of these concepts, including the roles of gene duplication, HGT, and gene fusion/fission. It also addresses the challenges in distinguishing orthologs from paralogs and the impact of lineage-specific gene loss and HGT on orthology and paralogy. The review highlights the importance of orthology in evolutionary genomics and the need for accurate identification methods, such as phylogenetic analysis and sequence similarity approaches, to disentangle orthologous and paralogous relationships. The discussion covers the complexities of orthologous clusters, the molecular clock hypothesis, and the emergence of xenologs, pseudoorthologs, and pseudoparalogs. The review emphasizes the significance of these concepts in understanding gene evolution and functional diversification.