We demonstrate applications of quantitative structure-property relationship (QSPR) modeling to supplement first-principles computations in materials design. We have here focused on the design of polymers with specific electronic properties. We first show that common materials properties such as the glass transition temperature (T g) can be effectively modeled by QSPR to generate highly predictive models that relate polymer repeat unit structure to T g. Next, QSPR modeling is shown to supplement and guide first-principles density functional theory (DFT) computations in the design of polymers with specific dielectric properties, thereby leveraging the power of first-principles computations by providing high-throughput capability. Our approach consists of multiple rounds of validated MQSPR modeling and DFT computations to optimize the polymer skeleton as well as functional group substitutions thereof. Rigorous model validation protocols insure that the statistical models are able to make valid predictions on molecules outside the training set. Future work with inverse QSPRs has the potential to further reduce the time to optimize materials properties. © 2012 Springer Science+Business Media, LLC.