The role of metformin as a preventative and therapeutic agent in lung cancer is beginning to be assessed. A recent epidemiological study from Taiwan demonstrated a 39-45% decreased risk of lung cancer in diabetic patients being treated with antidiabetic drugs including metformin versus those not taking these agents. These studies have triggered preclinical and clinical observational trials that further support metformin's potential as an antineoplastic agent. In a recent in vitro study, Ashinuma et al. was able to demonstrate inhibited clonogenicity, cell growth and proliferation in four different human lung cancer cell lines exposed to variable concentrations of metformin. These and other preclinical data have triggered in vivo experiments in mice. Memmott and colleagues showed that oral administration of 1 or 5mg/mL of metformin decreased lung tumor burden by 38% and 53% respectively in A/J mice injected with tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1 byutanone (NNK). Importantly, steady state levels of metformin were similar to those achieved in diabetic patients using metformin, suggesting the treatment and prevention of lung cancer could be achieved with standard oral dosing. Finally, two observational studies in humans have reinforced metformin's potential role as a therapeutic agent in lung cancer. In the first, Mezzone et al. showed that diabetic patients with lung cancer previously treated with metformin or thiazolidinediones had a lower incidence of metastatic disease at the time of diagnosis and a reduced risk of death compared to those who did not receive the same treatment. More recently, a retrospective study performed by Tan et al. evaluated the outcomes of three groups of diabetic patients with NSCLC treated with first line chemotherapy and receiving various diabetic drugs. In this study, patients treated with chemotherapy with metformin had superior outcomes compared to those patients treated with chemotherapy with insulin or with drugs other than metformin (OS, 20 months vs. 13.1 months vs 13.0 months, respectively, p=0.007). The remarkable activity of this agent in both preclinical and clinical lung cancer models as well as its low toxicity and tolerability in non diabetic patients warrants further prospective studies evaluating the therapeutic efficacy with platinum based chemotherapy in NSCLC.