At the 6th European Lung Cancer Conference (ELCC), held in Geneva, Switzerland, from 1316 April 2016, Suresh Ramalingam, MD, from The Winship Cancer Institute, Emory University, Atlanta, GA, discusses mechanisms of acquired resistance, including the C797S mutation, to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) that inhibit EGFR with T790M in patients with non-small cell lung cancer (NSCLC).