 Osomertanib is an effective treatment for EGF-immutant non-small cell lung cancer, NSCLC. However, some patients develop resistance to this drug. A new study has identified two main mechanisms of resistance to osomertanib, met amplification and EGF-RC797S mutations. Further research is needed to investigate other potential causes of resistance. This article was authored by Julianne Kolecki, Janelle E. Gray, Ying Cheng, and others.