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Although progress could have been achieved in treatment of patients with advanced non-small cell lung cancer (NSCLC), outcome still remains poor. One of the strategies to improve survival currently under investigation is maintenance therapy, e.g. prolongation of treatment duration with the administration of an agent at the end of a defined number of initial chemotherapy cycles. This can consist of molecularly targeted or chemotherapeutic drugs which were already included in the induction therapy or different, potentially noncross-resistant agents. The latter represents the perhaps most promising strategy according to currently available data. Drugs chosen for this form of maintenance should be well tolerated with favorable toxicity profile. In the search for this, pemetrexed has classified as an encouraging agent for maintenance therapy as it can be easily delivered, has a favorable toxicity profile and has already demonstrated significant efficacy in advanced NSCLC. Here we review the current status of maintenance therapy with emphasis on pemetrexed in advanced NSCLC. [ABSTRACT FROM AUTHOR]