Histone lysine methylation is a key epigenetic modification that plays a crucial role in various cellular processes, including gene expression, DNA replication, and chromatin structure. This review summarizes the enzymes responsible for histone lysine methylation and demethylation, as well as the biological roles of histone lysine methylation and the diseases associated with its misregulation. Histone lysine methylation is regulated by methyltransferases ('writers') and demethylases ('erasers'), which modify specific lysine residues on histones. These modifications are recognized by 'reader' proteins that interact with the methylated sites, influencing gene expression and chromatin structure. H3K4 methylation is involved in active transcription and is enriched at gene promoters. It is catalyzed by various methyltransferases, including the Set1/MLL family, which are regulated by subunits such as WRAD and unique subunits that interact with transcription factors. H3K4 demethylases, such as LSD1 and JARID1 family proteins, remove methyl groups from H3K4, affecting gene expression. H3K9 methylation is associated with heterochromatin and gene silencing, and is catalyzed by enzymes such as SUV39H1, SETDB1, and G9a. H3K9 demethylases, including JHDM2, JHDM3, and PHF8, remove methyl groups from H3K9, influencing gene expression and chromatin structure. H3K27 methylation is a hallmark of transcriptional repression and is catalyzed by the PRC2 complex, which includes EZH2. H3K27 demethylases, such as UTX, JMJD3, and PHF8, remove methyl groups from H3K27, affecting gene expression and chromatin structure. H3K36 methylation is involved in transcription elongation and is catalyzed by enzymes such as SETD2 and NSD1-3. H3K36 demethylases, including JHDM1 and JHDM3, remove methyl groups from H3K36, influencing gene expression and chromatin structure. H3K79 methylation is mediated by Dot1, which lacks a SET domain and is involved in chromatin structure and gene regulation. H3K79 methylation is regulated by H2B ubiquitylation, which enhances the activity of Dot1. Misregulation of histone lysine methylation is implicated in various diseases, including cancers and developmental defects. Understanding the mechanisms of histone lysine methylation is essential for developing therapeutic strategies targeting these modifications.Histone lysine methylation is a key epigenetic modification that plays a crucial role in various cellular processes, including gene expression, DNA replication, and chromatin structure. This review summarizes the enzymes responsible for histone lysine methylation and demethylation, as well as the biological roles of histone lysine methylation and the diseases associated with its misregulation. Histone lysine methylation is regulated by methyltransferases ('writers') and demethylases ('erasers'), which modify specific lysine residues on histones. These modifications are recognized by 'reader' proteins that interact with the methylated sites, influencing gene expression and chromatin structure. H3K4 methylation is involved in active transcription and is enriched at gene promoters. It is catalyzed by various methyltransferases, including the Set1/MLL family, which are regulated by subunits such as WRAD and unique subunits that interact with transcription factors. H3K4 demethylases, such as LSD1 and JARID1 family proteins, remove methyl groups from H3K4, affecting gene expression. H3K9 methylation is associated with heterochromatin and gene silencing, and is catalyzed by enzymes such as SUV39H1, SETDB1, and G9a. H3K9 demethylases, including JHDM2, JHDM3, and PHF8, remove methyl groups from H3K9, influencing gene expression and chromatin structure. H3K27 methylation is a hallmark of transcriptional repression and is catalyzed by the PRC2 complex, which includes EZH2. H3K27 demethylases, such as UTX, JMJD3, and PHF8, remove methyl groups from H3K27, affecting gene expression and chromatin structure. H3K36 methylation is involved in transcription elongation and is catalyzed by enzymes such as SETD2 and NSD1-3. H3K36 demethylases, including JHDM1 and JHDM3, remove methyl groups from H3K36, influencing gene expression and chromatin structure. H3K79 methylation is mediated by Dot1, which lacks a SET domain and is involved in chromatin structure and gene regulation. H3K79 methylation is regulated by H2B ubiquitylation, which enhances the activity of Dot1. Misregulation of histone lysine methylation is implicated in various diseases, including cancers and developmental defects. Understanding the mechanisms of histone lysine methylation is essential for developing therapeutic strategies targeting these modifications.