Lung cancer ranks top in both incidence and mortality in most part of the world. Scientists strive to explore biomarkers and their possible role in the diagnosis, treatment and prognosis of lung cancer. The ultimate goal is to discover biomarkers that can be tested in clinical trials and finally applied to patient care. Highly elevated concentrations of cytokeratin 19 fragment, tissue polypeptide antigen and squamous cell carcinoma antigen in non-small cell lung cancer particularly for squamous cell carcinoma, carcinoembryonic antigen and cancer antigen 125 in adenocarcinoma or non-small cell lung cancer, as well as progastrin-releasing peptide and neuron specific enolase in small cell lung cancer are suggestive biomarkers for the malignancy. Despite extensive studies, most results still remain controversial. Even with the report of high percent sensitivity and specificity, validation by clinical trials in large cohorts of patients is necessary before the cancer-related phenotypes can be translated into the clinic as reliable biomarkers. Nevertheless, identifications of biomarkers are leading to more understanding of the molecular pathways involved in lung cancer. It is hoped that understanding the connections between cellular pathways will help to reduce the suffering and loss of life caused by the lethal disease. This article summarizes the pre-clinical and translational researches against lung cancer in relation to biomarker discovery and validation. It is intended for policy makers, researchers, clinicians and other health professionals, offering a variety of useful biomarkers and updated data of clinical trials for lung cancer.