The concept of epigenetics has changed since it was first introduced in the 1940s by Conrad Waddington to describe "the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being". Nowadays, the meaning of epigenetics is accepted as the study of the heritable changes in the gene expression profile that do not entail a change in DNA sequence but modifies on the accessibility of the code via DNA methylation, modifications of amino acids on the aminoterminal tail of histones and non-coding RNAs. It has been proposed that these changes could be classified into three types: direct epigenetics, which occurs in the lifespan of a person; indirect epigenetics defines the ones that occur inside the womb due to events during gestation; and across indirect epigenetics, referred to those changes that affected the individual predecessors and somehow, maybe through changes in the gametes or intrauterine environment setting, are transmitted across generations. The immense interest in the field led to many studies showing the link between epigenetic changes and certain diseases such as diabetes, heart failure, cancer, inflammatory bowel diseases, and neurodegenerative diseases. Certain enzymes have been described as having a key role in these epigenetic modifications: DNA methyltransferases (DNMTs), in charge of the covalent addition of a methyl group to the DNA leading to the repression of certain genes; histone acetyltransferases (HATs) with the function of the acetylation of histone proteins, allowing the chromatin structure to open and become more transcriptionally active, and histone deacetylases (HDACs), which regulate the deacetylation of histones, leading to a hypoacetylation towards heterochromatin and gene suppression. Thus, the search for molecules that could hit these targets began, and the term "epidrugs'' was coined to describe chemical compounds that alter DNA and chromatin structure, promoting the disruption of transcriptional and post-transcriptional modifications by the inhibition of DNMTs and HDACs, mainly. As of 2022, several compounds have been approved by the Food and Drug Administration of the USA for clinical use, while other compounds are chemical probes.