Histone posttranslational modifications or PTMs are epigenetic marks. They have essential functions in multiple cellular systems, including transcription, DNA repair, and chromatin dynamics. Histone modifications regulate chromatin remodeling, thereby controlling gene expression or gene silencing. Alterations in histone modifications or PTMS due to histone modifiers, which are different classes of histone acetylase and histone deacetylases enzymes, develop cancer and other metabolic diseases. This chapter has given importance on methylation, acetylation, and ubiquitylation of histones. We have shown how these small molecules change the function of histones in developing cancer. We have also discussed various histone modifiers and their role in manipulating histone marks that increase or decrease the aggressiveness of cancer. This chapter has checked the importance of H3K4Me2/Me3, H3K27Me3, H4K12Ac, H4K16Ac, H4K27Ac, and H3K18Ac as a biomarker in different cancers, including glioma, hepatocellular carcinoma, gastric cancer, colorectal cancer, breast cancer, pancreatic cancer, and nonsmall cell lung cancer.