Simple SummaryNon-small cell lung cancer treatment has undergone a revolution in the past decade owing to the discovery of mutations that drive carcinogenesis and the development of molecular testing and treatments that act on them. Here, we detail the way in which lung cancer is currently diagnosed and treated in light of these developments. We focus on some of the key mutations for which targeted therapies have been developed and the trials that led to their approval. We hope to provide a comprehensive review of the current diagnosis and management of non-small cell lung cancer.AbstractTreatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift. Once a disease with limited potential therapies, treatment options for patients have exploded with the availability of molecular testing to direct management and targeted therapies to treat tumors with specific driver mutations. New in vitro diagnostics allow for the early and non-invasive detection of disease, and emerging in vivo imaging techniques allow for better detection and monitoring. The development of checkpoint inhibitor immunotherapy has arguably been the biggest advance in lung cancer treatment, given that the vast majority of NSCLC tumors can be treated with these therapies. Specific targeted therapies, including those against KRAS, EGFR, RTK, and others have also improved the outcomes for those individuals bearing an actionable mutation. New and emerging therapies, such as bispecific antibodies, CAR T cell therapy, and molecular targeted radiotherapy, offer promise to patients for whom none of the existing therapies have proved effective. In this review, we provide the most up-to-date survey to our knowledge regarding emerging diagnostic and therapeutic strategies for lung cancer to provide clinicians with a comprehensive reference of the options for treatment available now and those which are soon to come.