Lung cancer remains the leading cause of cancer death in men and women. Since the 1970s, there has been evidence for improved survival of women with lung cancer compared to men. Multiple analyses have demonstrated a survival advantage in women regardless of stage, histology, or treatment. The etiology for the improved prognosis is not yet fully elucidated, but is likely related to underlying biologic differences, including hormonal interactions. More recently, gender differences in response to newer agents such as epidermal growth factor receptor inhibitors and anti-angiogenesis agents have been identified. Further exploration of tumor molecular, biologic, hormonal, and pharmacogenomic interactions may provide additional insight into the observed survival benefit for women and, ultimately, permit exploitation of these differences in our treatment selection for both women and men.