At the time of diagnosis, half of lung cancer patientshave advanced incurable disease. Different chemotherapycombinations −with or without targeted therapies−yield similar results in spite of the continuousefforts of clinicians. However, molecular biologicalstudies have already shed a great deal of light on theexistence of multiple genetic aberrations that can beuseful for customizing treatment. mRNA transcriptsinvolved in DNA repair pathways, such as ERCC1and BRCA1, confer selective resistance to cisplatin ortaxanes. Polymorphisms in DNA repair genes andmethylation of checkpoint genes in circulating serumDNA could become important predictive markers ofsurvival to certain cisplatin-based regimens. EGFRtyrosine kinase mutations are the crux of targetedtherapies