Standard treatment of advanced non-small-cell lung cancer consists of platinum-based (doublet) polychemotherapy. The treatment should last for a maximum of four to six cycles. Several randomized clinical trials and some meta-analyses showed that a longer duration of treatment does not lead to an increase in survival. Recent data with new-generation agents (chemo- or targeted therapies) suggest that a maintenance treatment until progression of disease in patients with response or stable disease after the first cycles of induction (platinum-based) chemotherapy confers an advantage in time-to-progression or even overall survival (with pemetrexed) compared with no maintenance treatment. The advent of new agents and the better selection of patients according to histology or mutation of specific tyrosine kinase receptors (e.g., EGF receptor) seems to increase the therapeutic options and improve the prognosis in the advanced disease setting. The paradigm of the duration of therapy in advanced lung cancer appears to change from the use of second-line treatment only at progression of disease to an early introduction of an alternative (second-line) therapy as consolidation and chronic phase of maintenance.