Since the introduction of the term epigenetics by Conrad Waddington in 1942 to denote the mechanisms that relate genotype to phenotype, the term has been used with multiple meanings, going from the classic definition that refers to epigenetics as the study of the alterations in the biological phenotype without underlying changes in the DNA sequence, to one of the most recent and general definitions: "the structural adaptation of chromosomal regions to register, signal, or perpetuate altered activity states." At the molecular level, this adaptation involves the reversible modification of nucleic acids and histones. These modifications are catalyzed by a plethora of proteins, which could be considered as the core epigenetic targets, and that are classified into three main groups: (a) writers -enzymes capable of adding chemical groups to nucleic acids and histones -such as DNA methyltransferases (DNMTs), histone methyltransferases (HMTs) and histone acetyltransferases (HATs), (b) erasers -enzymes capable of removing marks introduced by the writers -such as histone deacetylases (HDACs) and histone demethylases (HDMs), and (c) readers -proteins with specialized domains capable of recognizing these changes -such as the bromodomain and external terminal protein (BET) family. In addition to these core epigenetic targets, a wide range of proteins also play important roles in epigenetic regulation; these proteins include histone chaperones (critical for nucleosome assembly), chromatin remodelers (CHRs -responsible for moving, ejecting, and restructuring the nucleosome), and even some classes of transcription factors. Epigenetics is an essential component in an organism's normal development and responsiveness, so its dysregulation has been associated with altered gene expression patterns related to multiple diseases. This makes epigenetic targets a significant focus for drug discovery research. Successful examples can be found in cancer research, with the approval of eight epigenetic drugs (drugs targeting epigenetic proteins) for clinical use: azacytidine and decitabine targeting DNMT1, vorinostat, belinostat, panobinostat, romidepsin and tucsibinostat targeting HDACs, and tazemostat targeting an HMT (EZH2). The importance of epigenetics in drug discovery is also illustrated by the increasing availability of chemogenomic databases related to epigenetics over the past decade. An example of this is EpiFactors, to the best of our knowledge, the database with the largest number of annotated proteins related to epigenetics reported so far, with a total of 815 different targets.