Lung cancer is the leading cause of cancer death among men and women in the United States with 170,000 deaths per year. This exceeds the sum of the next three leading causes of death due to cancer: breast, colon, and prostate. There are over 1 million deaths worldwide due to lung cancer, making it truly an epidemic. Fewer than 15% achieve a 5-yr survival. The vast majority (85%) present with advanced disease, although stage I patients may have a 5-yr survival approaching 70% (1). 80% of the lung cancers are non-small cell lung cancer (NSCLC; adenocarcinomas, squamous cell, bronchoalveolar and large cell carcinomas) and 20% are small cell lung cancer (SCLC). Cigarette smoking constitutes 80% of the attributable risk and asbestos, radon, other occupational and environmental exposures and genetic factors contribute to the rest. The purpose of this state of the art review is to introduce the molecular genetics of lung cancer for the clinician in this rapidly progressing fi eld. Many of the basic science concepts to follow already are being studied in clinical trials of new chemotherapeutic agents or gene therapy.