We recently traveled to Austin, Texas, for a State of the Science Summit™ on Lung Cancer. Immunotherapy, whether alone or in combination with chemotherapy, has become a frontline standard of care in advanced non–small cell lung cancer. While PD-L1 expression and the presence of molecular markers such as ALK and EGFR can help determine whether such an approach is recommended, results from PD-L1 testing and next-generation sequencing can take several weeks to return. In the context of a symptomatic patient who cannot wait for the results to return before beginning treatment, what is the optimal treatment, and can a liquid biopsy hasten the process? Additionally, in a patient with brain metastases who has been treated with targeted therapy and local therapy, should immunotherapy be used as the next line of therapy?