This section is organized into three major parts. First, we described the results of the data sets of epigenetic targets used in this work. The second part, entitled "Epigenetic Target Prediction with Machine Learning," presents the results of the development of the machine learning models and their validation using two main strategies. The third main section, "Retrospective Identification of Epigenetic Targets," shows, as a case study, a practical application of the best machine learning model derived in the second part, to identify epigenetic targets for external and recently reported compounds. All the details of the methods used are described in the Experimental Section.