Until recently, first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) was based on ASCO guidelines. Since several years, first-line chemotherapy is a platin-based doublet for patients with a good performans status. For elderly or unfit patients, a single-drug chemotherapy or a combination without cisplatin was recommended. The association of an anti-angiogenic therapy, bevacizumab, with carboplatin-paclitaxel or cisplatin-gemcitabine regimens improves progression-free survival for patients with non-epidermoid tumors. The combination of cisplatin and pemetrexed is better in terms of survival than cisplatine-gemcitabine in these tumors. The choice of treatment according to histology is becoming a new concept. Another is maintenance therapy. The main objective is to reduce duration of platin-based chemotherapy while improving quality of life and progression-free survival. This concept is ongoing validation. The combination of cetuximab with platin-chemotherapy improves survival for all histologic types. We should integrate this new approach among other available treatments. First-line therapy for advanced NSCLC is changing. In the future, first-line therapy will be chosen according to clinical features and biomarkers such as gene mutations of EGFR.