Non-small cell lung cancer (NSCLC) is a common malignant disease with an extremely poor prognosis. Chemotherapeutic treatment for advanced disease is currently based on histological subtyping, but recent discoveries of genetic alterations in subsets of NSCLC have already changed clinical practice with regard to Egfr mutations as predictive markers of response to gefitinib and erlotinib. This has also paved the way for the integration of molecular analyses into early phase clinical trials, as demonstrated by the clinical development of crizotinib, effective in lung cancer harbouring Alk rearrangements. Similarly, other subgroups of NSCLC carry potentially targetable molecular alterations and their study has the potential to change the diagnostic and therapeutic approach to lung cancer in the near future. In contrast to a wealth of knowledge surrounding genomic alterations in lung adenocarcinomas, fewer data are available concerning squamous cell lung cancer (SCC), although recent data demonstrate that genotyping can provide new therapeutic perspectives in SCC treatment. Moreover, the study of molecular predictive markers of response to chemotherapy aims to improve chemotherapeutic treatment, increasing efficacy and limiting toxicity.