Purpose: To provide consensus recommendations on the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIS) in patients with advanced or meta-static non-small-cell lung cancer (NSCLC). Methods: Using a systematic literature search, phase II trials, randomized phase III trials, and meta-analyses were identified for inclusion. Results: A total of forty-six trials were included. Clear evidence is available that EGFR-TKIS should not be administered concurrently with platinum-based chemotherapy as first-line therapy in advanced or metastatic NSCLC . Evidence is currently insufficient to recommend single-agent EGFR-TKIS as first-line therapy either in unselected populations or in populations selected on the basis of molecular or clinical characteristics. Following failure of platinum-based chemotherapy, the evidence suggests that second-line EGFR-TKIS or second-line chemotherapy result in similar survival. Quality of life and symptom improvement for patients treated with an EGFR-TKI appear better than they do for patients treated with second-line docetaxel. Sequence of therapy may not appear to be important, but if survival is the outcome of interest, the goal should be to optimize the number of patients receiving three lines of therapy. Based on available data, molecular markers and clinical characteristics do not appear to be predictive of a differential survival benefit from an EGFR-TKI and therefore those factors should not be used to select patients for EGFR-TKI therapy. Conclusions: The EGFR-TKIS represent an additional therapy in the treatment of advanced or metastatic NSCLC. The results of ongoing clinical trials may define the optimal role for these agents and the effectiveness of combinations of these agents with other targeted agents.