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Non-small cell lung cancer (NSCLC) has made a remarkable development in recent decades with respect to its perception. In the late 1990s it was the "problem child" as the main cause of cancer with increasing tendencies, especially in women and with a pronounced stigmatization. It is now the role model as a biologically rational targeted treatment based on molecular dependencies of the tumor with a vast improvement of the traditionally poor survival times. Molecular tumor boards have long followed the NSCLC example in the assessment of targeted treatment approaches for other tumor entities. This review article gives an overview of the current possibilities for targeted treatment of NSCLC, which nowadays are applicable for nearly one third of all patients with NSCLC., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)