A better understanding of the molecular physics underlying π-π interactions is important for rational design of supramolecular structures, and our data present a clear roadmap for those looking to rationalize and utilize such interactions. Consideration of electron-donating or withdrawing effects within the context of the Hunter-Sanders rules is not an effective guide and one should look instead to the "direct interaction model" of Wheeler and Houk to explain substituent effects on stacking energies. At the same time, our work suggests that substituent modifications alone may be insufficient to avoid offsetstacking in supramolecular frameworks and other soft materials.