The article reviews the key protein families that mediate epigenetic signaling through the acetylation and methylation of histones, including histone deacetylases, protein methyltransferases, lysine demethylases, bromodomain-containing proteins, and proteins that bind to methylated histones. These protein families are emerging as druggable targets for treating various diseases such as cancer, inflammation, metabolic disorders, and neuropsychiatric disorders. The article discusses the known links between these proteins and diseases, the basic molecular mechanisms of action, and recent progress in pharmacological modulation. It highlights the dynamic nature of epigenetics and the potential for altering disease-associated epigenetic states through direct manipulation of the molecular factors involved. The review also covers the structural and functional aspects of these protein families, including their roles in chromatin remodeling, transcriptional regulation, and disease pathways. Finally, it discusses the challenges and opportunities in developing selective inhibitors for these proteins, emphasizing the importance of understanding their interactions within multiprotein complexes.The article reviews the key protein families that mediate epigenetic signaling through the acetylation and methylation of histones, including histone deacetylases, protein methyltransferases, lysine demethylases, bromodomain-containing proteins, and proteins that bind to methylated histones. These protein families are emerging as druggable targets for treating various diseases such as cancer, inflammation, metabolic disorders, and neuropsychiatric disorders. The article discusses the known links between these proteins and diseases, the basic molecular mechanisms of action, and recent progress in pharmacological modulation. It highlights the dynamic nature of epigenetics and the potential for altering disease-associated epigenetic states through direct manipulation of the molecular factors involved. The review also covers the structural and functional aspects of these protein families, including their roles in chromatin remodeling, transcriptional regulation, and disease pathways. Finally, it discusses the challenges and opportunities in developing selective inhibitors for these proteins, emphasizing the importance of understanding their interactions within multiprotein complexes.