Lung cancer is a challenging clinical problem worldwide and it is the leading cause of death from cancer for both men and women. Because of this, the ability to diagnose lung cancer in its early stages is considered crucial to achieve decreased lung cancer mortality. Proteomics has recently been introduced to the field of cancer research, and its potential applications are just beginning to be understood. Unlike the study of a single protein, proteomic technology offers a systemic overview that provides the potential to improve our understanding of lung cancer. Two proteomic approaches are currently being used for lung tissue; matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF) and surface-enhanced laser desorption/ionization (SELDI). Several groups have reported that detection of unique protein peaks can be used to accurately identify pre-malignant lesions, tumor classes and the behavioral aspects of tumors such as the proclivity to metastasize; such proteins involved include translation elongation factor-1 delta, 14-3-3, small ubiquitin-related modifier-2 and thymosin-4. Proteomics may have the potential to detect early changes in dysplastic lesions that predispose them to malignant transformation. In this review, these perspectives on the molecular targets for early detection of lung cancer will be discussed and summarized.