Epigenetic modifications are controlled by distinct modulators (writers, erasers, remodelers, and readers) that dynamically regulate chromatin structure and gene expression. In this issue, Honer et al. review how these chromatin and DNA modifiers work and their contributions to human disease. The illustration represents the chromatin structure, with its simplest subunit, the nucleosome, composed of histone proteins (purple) and DNA (blue), coming from a nucleus that was spectral-karyotyped for each chromosome. The epigenetic factors controlling the chemical modifications (yellow), either on the histones or on the DNA, are also shown as irregular clusters in various colors. The 3D graphic of the chromatin and DNA structures was designed by Iris Joval, and the epigenetic modifiers were designed in BioRender and modified with Adobe Photoshop. The final image was designed and assembled by Johnathan R. Whetstine. (For details, see Honer et al., p. 473.)