The article reviews the mechanisms by which chromatin-binding modules interpret histone modifications, focusing on the recognition of acetylation and methylation marks. It highlights the structural and functional insights into how these modifications are read by 'reader pockets' or effector modules, which play crucial roles in regulating chromatin structure and function. The review discusses the diverse families of reader pockets, including bromodomains, chromodomains, PHD fingers, and tudor domains, and their specific interactions with histone modifications. It also explores the implications of these interactions for gene expression, epigenetic inheritance, and human diseases, particularly cancer. The article emphasizes the importance of understanding how these modifications are translated into biological outputs and the potential for engineering these modules to alter their specificity.The article reviews the mechanisms by which chromatin-binding modules interpret histone modifications, focusing on the recognition of acetylation and methylation marks. It highlights the structural and functional insights into how these modifications are read by 'reader pockets' or effector modules, which play crucial roles in regulating chromatin structure and function. The review discusses the diverse families of reader pockets, including bromodomains, chromodomains, PHD fingers, and tudor domains, and their specific interactions with histone modifications. It also explores the implications of these interactions for gene expression, epigenetic inheritance, and human diseases, particularly cancer. The article emphasizes the importance of understanding how these modifications are translated into biological outputs and the potential for engineering these modules to alter their specificity.