This review focuses on the latest updates in the field of EGFR-mutant advanced NSCLC treatment, addressing the EGFR-dependent and independent mechanisms of resistance to EGFR-TKIs, including MET and HER gene amplifications, the role of mutations coding for the RAS and PIK3CA genes, as well as other less common genetic alterations. This evidence concerns the gene EGFR and non-small cell lung carcinoma.