Erlotinib, a tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR), was licensed for maintenance therapy after first-line chemotherapy and after failure of at least one prior chemotherapy regimen for non-small cell lung cancer. In July 2011, the Committee for Medicinal Products for Human Use of the EMA recommended an extension of indication for erlotinib as first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR activating mutations. Two phase III trials were found for this indication, both showing improved outcomes for progression free survival for patients treated with erlotinib in comparison to standard platinum-based chemotherapy. Despite distinct differences, toxicity profiles were also more favourable for erlotinib. However, no information regarding impact on overall survival was available and data for quality-of-life were very limited. Open questions concern methods for determining EGFR mutation status as well as characteristics associated with resistance to erlotinib.