Lung cancer is a worldwide epidemic and despite platinum-based chemotherapy being the cornerstone of non-small cell lung cancer treatment, patient response rates to these regimens remain very low. Although resistance to cisplatin is multifactorial, DNA repair plays a critical role in cisplatin resistance. One of the most important goals in translational research is to investigate the clinical use of DNA repair pathways that may influence cisplatin chemosensitivity. Trying to understand the role of genes involved in DNA repair and response to treatment has become one of the main objectives of individualised chemotherapy. It is well known that chemosensitivity is individually predetermined, and the upregulation of mRNA transcripts has been linked to differential response to cytotoxic drugs. In this article, the authors try to highlight the more relevant aspects regarding these issues, primarily focused on the potential role of ERCC1, RRM1, XPD and BRCA1 expression profiling as predictors of anticancer drug efficacy.