Destructive quantum interference in aromatic hydrocarbons can be tuned using chemical substituents; however, classical chemical intuition is not enough to explain the effects on electron transport. Using Huckel theory and density functional theory calculations, in combination with the Landauer–Buttiker approach for charge transport, novel substituent effects are demonstrated. For a 1,3-linked benzene, an electron acceptor in position 2 is shown to have the same effect on the antiresonance energy as an electron donor in position 4 and vice versa. Substituents in position 5 have no effect on the antiresonance energy. The effects appear to be additive, such that a donor in position 2 will counteract a donor in position 4, leading to cancellation of the substituent effect. Counter- and nonactive substituent positions exist for all aromatic hydrocarbons and can be predicted using a diagrammatic approach. This insight should be useful when substituents are to be used for tuning destructive quantum interference ...