During recent years, we have seen an increasing awareness among physicians about the possibilities of helping patients stricken by non-small cell lung cancer using active intervention with chemotherapeutics. This has emerged mainly from the development of new chemotherapeutics and novel drug combinations with an improved therapeutic ratio better tolerated by the patients. However, these new combinations of chemotherapeutics have proved to be only marginally better in terms of survival than the earlier used cytotoxic agents. Thus, many clinicians consider the effects of systemic therapy on symptom control and improved quality of life to be at least as important as survival when evaluating new drugs or new combinations. It is also obvious that improvements using traditional cytotoxics are slow and that there is a need for novel approaches. The present review focuses on novel drugs that have recently been introduced, or soon await to be included, in the management of advanced lung cancer and which have a potential value for use in neoadjuvant treatment of patients with non-small cell lung cancer, i.e. pemetrexed, EGFR-inhibiting agents, anti-angiogenesis inhibitors and other small molecules.