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Precision medicine has revolutionized lung cancer management – particularly non-squamous cell carcinomas – with a broader genomic comprehension and the possibility of offering tailored treatments guided by oncogenic driver mutations – the basis of precision medicine. Since the publication of the IPASS trial in 2009 a new Era of molecular actionability began for lung cancer research and treatment. The remarkable past fifteen years were characterized by advances on genomic testing methodologies, the emergence of new biomarkers and targeted therapies, and the widespread of precision medicine in lung cancer care from advanced to earlier stages – specially for the adenocarcinoma histology, a heterogeneous disease with unprecedent improvements in outcomes. Nonetheless, several barriers need to be overcome with the adoption of cutting-edge technologies, such as the high cost of new diagnostic and therapeutical technologies and their discrepant accessibility, mainly in low- and middle-income countries. Moreover, there is still a lack of clear clinical actionability for squamous cell carcinoma and small cell lung cancer in which ideal biomarkers are yet to be discovered and validated. Herein, we aimed to discuss several aspects on how precision medicine positively impacted on lung cancer management and the lessons learned. Additionally, we scoped future perspectives on precision oncology in lung cancer as technology advances.