Platinum doublets are the recommended standard first-line chemotherapy for stage IIIB/IV non-small-cell lung cancer (NSCLC). As efficacy outcomes associated with currently approved agents (cisplatin and carboplatin) are broadly similar, the decision about which platinum-based doublet to use is based on other factors such as toxicity. The goals for new platinum agents are to maintain and perhaps improve current efficacy and to improve toxicity. The aim of this article is to review the available clinical data from studies investigating the third-generation platinum analogue oxaliplatin in patients with advanced NSCLC. Information was obtained from the PubMed database and from recent presentations at national and international meetings. Oxaliplatin has been studied as monotherapy and in combination with a wide range of other chemotherapies (vinca alkaloids, taxanes, gemcitabine, and pemetrexed), mainly in phase II trials. Preliminary results from studies in which oxaliplatin-based doublets have been combined with targeted agents (eg, bevacizumab) are now available. In general, the clinical activity observed with oxaliplatin-based therapy is similar to that seen with other currently used platinum regimens, although outcomes vary between individual trials (response rates, 23%-48%; median progression-free survival, 2.7-7.3 months; median overall survival, 7.3-13.7 months). The toxicity profile of oxaliplatin, particularly when compared with cisplatin, makes it an alternative treatment, especially in patients unable to tolerate cisplatin. However, well-conducted randomized phase III trials will be needed to clarify which particular groups of patients with NSCLC may benefit from oxaliplatin-based therapy.