Resistance to epidermal growth factor receptor (EGFR) inhibitors in patients with non-small-cell lung cancer (NSCLC) is often caused by acquisition of the T790M mutation in EGFR (EGFR-T790M). Walter et al. have developed a kinase inhibitor, CO-1686, that effectively inhibits EGFR-T790M without affecting wild-type EGFR. CO-1686 reduced tumour growth in several preclinical models of NSCLC, including transgenic mice expressing mutant EGFR and xenograft models. CO-1686 is being tested in Phase I/II clinical trials for EGFR-mutant NSCLC.