Epidermal growth factor receptortyrosine-kinase inhibitors (EGFR-TKIs) have elicited curative effects on patients with advanced non-small celllung cancer and with activating mutations in the EGFR gene. However, acquired resistance to EGFR-TKIs is eventually developed after an initial response is induced;as such, patients with acquired resistance must be treated with more ef-fective strategies to delay or possibly overcome the resistance. This article reviews available data on the treatment of patientswho have failed to respond to EGFR-TKI.