Lung cancer is the leading cause of cancer-related death in the world. Prior to 
the era of targeted therapy, platinum-based doublet chemotherapy was the 
first-line therapy of choice for patients with metastatic non-small-cell lung 
cancer (NSCLC). The availability of agents that target epidermal growth factor 
receptor (EGFR)-tyrosine kinase, as well as inhibitors against anaplastic 
lymphoma kinase (ALK) gene rearrangement or ROS-1 gene rearrangement product, 
has provided promising clinical benefits in specific subpopulations of NSCLC. At 
present, only first-generation EGFR-tyrosine kinase inhibitors (TKIs) (erlotinib 
and gefitinib) are available for clinical use. Second-generation irreversible 
EGFR-TKIs, such as afatinib, are still in clinical trials. In current clinical 
practice, EGFR-TKI is the first-line treatment of choice for metastatic NSCLC 
patients with tumor EGFR mutation or as salvage therapy in NSCLC patients who 
received systemic chemotherapy previously. Platinum-based doublet chemotherapy 
continues to be the standard of care for those treatment-naïve patients with 
EGFR wild -type tumor or unknown EGFR status. Even though all investigators 
agree with the use of EGFR-TKI as the first-line treatment in tumor EGFR-mutated 
patients, only 10-30% of NSCLC patients have mutated EGFR, and there was no 
obvious survival difference when EGFR-TKIs were used in a second-line setting 
versus a first-line treatment in EGFR-mutated patients. Thus, the molecular 
complexity of lung cancer emphasizes the need for optimizing treatment by 
seeking a more personalized approach to care, including searching for driver 
oncogenes, managing the emergence of resistance and overcoming that resistance, 
and optimizing the sequence of treatment. Numerous other novel targeted agents 
are now in clinical development, including new agents targeting novel pathways 
and those that may have the potential to overcome the limitations or resistance 
associated with currently available EGFR-TKIs. In this report, we review the 
clinical data of EGFR-TKIs as molecular-targeted therapies in NSCLC.