Histone methylation reader proteins (HMRPs) regulate gene transcription by recognizing, at their “aromatic cage” domains, various Lys/Arg methylation states on histone tails. Since epigenetic dysregulation underlies a wide range of diseases, HMRPs have thus become attractive drug targets. However, structure-based efforts in targeting them are still in their infancy. Structural information from functionally unrelated aromatic-cage-containing proteins (ACCPs) and their co-crystallized ligands could be a good starting point. In this light, we mined the PDB to retrieve the structures of ACCPs in complex with cationic peptidic/small-molecule ligands. Our analysis revealed that the vast majority of retrieved ACCPs belong to three classes: transcription regulators (chiefly HMRPs), signaling proteins, and hydrolases. While acyclic (and monocyclic) amines and quats are the typical cation-binding functional groups found in HMRP small-molecule inhibitors, numerous atypical cationic groups were identified in non-HMRP inhibitors, which could serve as potential bioisosteres to methylated Lys/Arg on histone tails. Also, as HMRPs are involved in protein-protein interactions, they possess large binding sites, and thus their selective inhibition might only be achieved by large and more flexible (beyond-rule-of-five) ligands. Hence, the ligands of the collected data set represent suitable versatile templates for further elaboration into potent and selective HMRP inhibitors.