The identification of actionable oncogenic driver mutations in patients with non-small cell lung cancer impacts therapy selection, and appropriate therapy administration results in improvements in clinical outcomes. Although biomarker testing for actionable oncogenic driver mutations is recommended in national and international guidelines, there are still unmet needs in the real world. Through this podcast we provide, from a US perspective, an overview and discuss challenges in biomarker testing from both an academic and a community oncologist viewpoint. We describe the importance of comprehensive testing, actionable biomarkers as recommended by guidelines such as National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology, types of tests and assessment techniques for detection of actionable biomarkers, and challenges in testing. These challenges include the lack of awareness of the biomarker testing guidelines among physicians, inconsistent reimbursement, longer turnaround time resulting in delays in therapy initiation, and nihilism associated with particular patient characteristics. To tackle these challenges, we offer recommendations from the perspective of our own clinical settings.