Selective kinase inhibitors---such as the blockbuster drug imatinib---have shown tremendous promise in the treatment of cancers involving kinase dysregulation. Currently, over 27 small molecule targeted kinase inhibitors have received FDA approval, representing a substantial fraction of the $37B U.S.~market for oncology drugs. Despite this, major challenges remain in their widespread application in cancer treatment. To meet these challenges, our laboratory develops quantitative physical models of kinase inhibitor efficacy to accelerate the rational design of kinase inhibitors with desired selectivity profiles, an understanding of mutational mechanisms of resistance, and prediction of drug sensitivity and resistance in individual patient tumors.