Cytotoxic therapy for lung-cancer patients has only moderately improved during the last decades. Simultaneously, efforts of intensive research to increase our understanding of the molecular basis of lung cancer have been undertaken. The cancer cell has been characterised by several genetic changes that lead to altered cellular functions. In addition, multiple factors of the cancer-cell environment further affect the tumour cell via various receptors and subsequent signaling pathways. The increased knowledge of cellular signaling offers the opportunity to develop novel substances that target specific pathway molecules. In the current review, some of the most essential receptors and signaling pathways involved in lung cancer will be described. In conjunction, examples of novel target-specific agents that have already found their way into clinical trials will be discussed.