Computer-aided drug design (CADD) has been credited to the modern patterns in compound characterization in drug discovery . It represents an advancement when compared to HTS as it requires minimal compound design or prior knowledge, but can yield multiple hit compounds among which promising candidates have been elected. The typical role of CADD in drug discovery is to screen out large compound libraries into smaller clusters of predicted active compounds. CADD has become an indispensable tool to accelerate the development of epigenetic inhibitors helping in the selection, design, and lead identification of novel compounds. LBDD approaches employ the chemical structures of experimentally established epigenetic inhibitors to conduct SAR studies. From this, chemoinformatics and similarity tools have been used to identify new epigenetic inhibitors by searching in commercial and focused databases.