Lung cancer presents a major health problem in the world, with the highest rates seen in North America and northwestern Europe.1– During 2001, 169,500 new cases were presented in the United States, with 157,400 people dying of lung cancer.2– In fact, more people die from lung cancer than of colon, breast, and prostate cancers combined.3– Non-small cell lung cancers (NSCLCs) [adenocarcinoma, squamous cell carcinoma, large cell anaplastic carcinoma, and undifferentiated carcinomas] represent approximately 80% of all lung carcinomas. Of patients with NSCLC, surgery is the preferred option for resectable cases, providing success in only one fourth of patients due to frequent recurrence. Similarly, chemotherapy, which is used in advanced disease, provides limited survival and has considerable toxicity.4– Unfortunately, the most common NSCLC subtype, adenocarcinoma, has usually metastasized before clinical symptoms become apparent, thereby reducing treatment options and ensuring a poor outcome.5– Despite intensive research, the overall 5-year survival rate is only 8 to 14%, and has improved marginally during the past 25 years.6 Novel approaches for the management of lung cancer are urgently needed. Enormous efforts have been made to identify risk factors associated with the development of lung cancer and to explore potential preventive therapies. One such potential therapeutic target is the cyclooxygenase (COX) enzyme. Recent evidence suggests an important role of the inducible COX-2 isoform during the development of lung cancer.6 Precursor lesions express high levels of COX-2, COX-2 expression is associated with poor prognosis, and early data imply the use of selective COX-2 inhibitors may provide some benefit for prevention and/or treatment of lung cancer. This review will discuss the current role of COX-2 in lung cancer and how selective targeting may prove to add benefit for the treatment of lung cancer.