Lung cancer is a collection of rare diseases, each with its specific genomic abnormalities. Next generation sequencing is a novel diagnostic tool to discover driver mutations. This technology, together with the development of targeted drugs, is rapidly changing our understanding of lung cancer. KRAS gene mutations are the most common mutation in adenocarcinoma of the lung. Patients with ALK rearrangements treated with specific ALK inhibitors such as crizotinib or EGFR-activating mutations treated with gefitinib, erlotinib or afatinib have improved progression-free survival and better quality of life than patients treated with chemotherapy. The latter may subsequently develop tumour resistance, for which novel drugs are rationally designed. In the Netherlands, multidisciplinary tumour boards guide the interpretation of genomic aberrations and the use of registered and off-label targeted drugs.