Lung cancer is the leading cause of cancer related deaths. Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers. Our understanding of driver mutations and genotype directed therapy has revolutionized the management of advanced NSCLC. Commonly described mutations include mutations in epidermal growth factor (EGFR) & BRAF and translocations in anaplastic lymphoma kinase (ALK) & rat osteosarcoma (ROS1). Drugs directed against these translocations have significantly improved progression free survival individually and have shown a survival benefit when studied in the Lung Cancer Mutation Consortium (median survival 3.5 vs. 2.4 years compared to standard therapy). In a related yet parallel universe, the number of bronchoscopic ablative modalities available for management of cancer related airway obstruction have increased exponentially over the past decade. A wealth of literature has given us a better understanding of the technical aspects, benefits and risks associated with these procedures. While they all show benefits in terms of relieving airway obstruction, symptom control, quality of life and lung function testing, their complication rates vary based on the modality. The overall complication rate was ~4% in the AQuIRE registry. Bronchoscopic therapeutic modalities include rigid bronchoscopy with mechanical debulking, laser, thermo-coagulation [electrocautery & argon plasma coagulation (APC)], cryotherapy, endobronchial brachytherapy (EBT), photodynamic therapy (PDT), intratumoral chemotherapy (ITC) and transbronchial needle injection (TBNI) of chemotherapy. Intuitively, one would assume that the science of driver mutations would crisscross with the science of bronchoscopic ablation as they overlap in the same patient population. Sadly, this is not the case and there is a paucity of literature looking at these fields together. This results in several unanswered questions about the interplay between these two therapies.