Isoindigo and derivatives thereof were synthesized and characterized by means of differential pulse voltammetry (DPV) and UV-vis absorption and fluorescence spectroscopies. The experimental results were compared with the results of density functional theory (DFT) calculations to provide structure property relationships on the basis of the type of substituent and attachment position (5,5' vs 6,6') on isoindigo. The integration of if-electron donors mainly affects the ionization potential (IP) as the isoindigo unit dictates the electron affinity (EA). The incorporation of electron withdrawing groups affects the EA through contributions of and if-effects that depend on the electron deficiency of the substituent. Perspectives on the photostability of isoindigo and its derivatives are presented along with a discussion about the relation between substitution pattern and the strength of the optical transitions. Functionalization of the 5(5') carbon in isoindigo leads to a smaller transition dipole moment when compared to substitution on carbon 6(6'), while having a small effect on the frontier orbital energies. These observations enhance our understanding of the electronic structure and optical properties of isoindigo and permit important advances in the establishment of unambiguous design parameters for the next generation of isoindigo-based oligomers and polymers.