Erlotinib and gefitinib are tyrosine kinase inhibitors (TKI) associated with the EGFR, which is involved in cell proliferation, growth, migration, invasion and survival, and has been found to be overexpressed in non-small-cell lung cancer. Erlotinib was the first target agent approved for the treatment of NSCLC in second- and third line, in patients unselected for EGFR mutations; gefitinib was the first EGFR tyrosine kinase inhibitor approved for the treatment of NSCLC in all lines of setting in patients harbouring EGFR mutations. In elderly patients, with a poor prognosis, and different co-morbidities, erlotinib and gefitinib could be considered as valid therapeutic options. This paper reviews the role of both drugs, in the management of elderly patients affected by advanced NSCLC based on an update analysis of randomised and non-randomised clinical trials.