Tyrosine kinase inhibitors of the epidermal growth factor receptor, gefitinib and erlotinib, have changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). Many phase II or III studies have proven the efficacy of gefitinib or erlotinib as the first-line, second-line, or third-line treatment. However, it is not clear whether gefitinib or erlotinib has different activities in advanced NSCLC patients with different clinicopathological features or at different stages. We review the published clinical trials that used gefitinib or erlotinib in NSCLC and compare their efficacy. The selection criteria and efficacy measurement in these trials that might affect the final results of the studies are listed and discussed. The adequate-powered, direct comparisons of gefitinib against erlotinib under the same clinical scenarios are lacking. There is no evidence at present that the efficacy of these two agents in NSCLC is different.