Lung cancer is the deadliest form of cancer in the world and is most commonly associated with smoking. Current treatment strategies are largely ineffective due to advanced stage at diagnosis and the inherent therapeutic resistance of lung cancer cells. To improve patient outcomes, many studies have been designed to identify molecular alterations in lung cancer in order to develop new therapeutic strategies. Molecular alterations in lung cancer include genetic changes, epigenetic changes, and changes in the expression or activity of kinases that comprise signaling pathways within cells. Signaling pathways are attractive targets for lung cancer therapy because activation of signaling pathways contributes to tumor growth and therapeutic resistance, and constitutively active signaling commonly occurs in lung cancer. This review will discuss signaling pathways that are relevant to lung cancer. We will discuss specific signaling aberrations found in lung cancers, review the status of signaling inhibitors being developed for lung cancer, identify emerging targets, and provide recommendations for the development of agents designed to inhibit signal transduction.