The pathological diagnosis of lung cancer has transformed over the past several years from a morphological characterisation of the disease to one where molecular characterisation has become increasingly important. Molecular characterization of lung carcinoma contributes valuable information in terms of diagnosis, prognosis, and the potential for treatment with targeted therapy. Hence, the simple separation of lung cancer into small cell and non-small cell is insufficient for the modern day management of this cancer. Over the past few decades, the concept of “oncogene addiction” in malignancies has led to the documentation of a number of reproducible molecular alterations in lung cancer- the so called “driver mutations”. This has permitted the identification of specific molecular cohorts of patients who may benefit from therapy targeted at these driver mutations. Among other challenges for the pathologist of today is the demand to extract a vast body of information from increasingly small diagnostic specimens and scanty cell aspirates. The pathologist plays a pivotal role in balancing the need to preserve tissue for molecular studies, over performing other ancillary, potentially wasteful studies. With additional evidence that targeted therapy is a major improvement over conventional chemotherapy when applied to the appropriately selected patients, evaluation for epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) and ROS-1 rearrangements are now considered by many to be the standard of care in advanced-stage pulmonary adenocarcinomas. Personalized precision medicine is real, and is here, and having a firm grasp of the processes involved in molecular testing of tumour specimens should be an overriding concern for the pathologist. As more sophisticated and sensitive testing modalities evolve, it behoves the astute practicing pathologist to remain ‘future-proof’ and relevant in facing the challenges ahead.