Histone modifications regulate chromatin structure and function, playing key roles in DNA manipulation and expression. Histone post-translational modifications (PTMs) include acetylation, phosphorylation, methylation, ubiquitylation, sumoylation, deimination, and ADP ribosylation. These modifications influence chromatin structure and function by altering histone interactions with DNA and recruiting enzymes that modify chromatin. Acetylation neutralizes histone charges, weakening interactions with DNA and promoting transcription. Phosphorylation affects chromatin structure and is involved in DNA repair and replication. Methylation, which does not alter histone charge, can be mono-, di-, or tri-methylated on lysines or arginines. Ubiquitylation and sumoylation modify chromatin structure and function, while tail clipping removes modifications entirely. Histone modifications also regulate the binding of chromatin factors, such as through bromodomains, PHD fingers, and chromodomains. These modifications can interact with each other (cross-talk) to fine-tune chromatin regulation. Genomic localization of modifications varies, with euchromatin being more relaxed and heterochromatin more compact. Heterochromatin includes facultative and constitutive types, with constitutive heterochromatin being permanently silenced. Euchromatin contains active genes and modification-rich regions. Histone modifications are involved in cancer development, with dysregulated modifications linked to gene expression changes and genome instability. Epigenetic drugs, such as HDAC inhibitors, show promise in cancer treatment. Future research aims to uncover more histone modifications and their functions, as well as the mechanisms of histone modification delivery and control by RNA.Histone modifications regulate chromatin structure and function, playing key roles in DNA manipulation and expression. Histone post-translational modifications (PTMs) include acetylation, phosphorylation, methylation, ubiquitylation, sumoylation, deimination, and ADP ribosylation. These modifications influence chromatin structure and function by altering histone interactions with DNA and recruiting enzymes that modify chromatin. Acetylation neutralizes histone charges, weakening interactions with DNA and promoting transcription. Phosphorylation affects chromatin structure and is involved in DNA repair and replication. Methylation, which does not alter histone charge, can be mono-, di-, or tri-methylated on lysines or arginines. Ubiquitylation and sumoylation modify chromatin structure and function, while tail clipping removes modifications entirely. Histone modifications also regulate the binding of chromatin factors, such as through bromodomains, PHD fingers, and chromodomains. These modifications can interact with each other (cross-talk) to fine-tune chromatin regulation. Genomic localization of modifications varies, with euchromatin being more relaxed and heterochromatin more compact. Heterochromatin includes facultative and constitutive types, with constitutive heterochromatin being permanently silenced. Euchromatin contains active genes and modification-rich regions. Histone modifications are involved in cancer development, with dysregulated modifications linked to gene expression changes and genome instability. Epigenetic drugs, such as HDAC inhibitors, show promise in cancer treatment. Future research aims to uncover more histone modifications and their functions, as well as the mechanisms of histone modification delivery and control by RNA.