AbstractPurpose of ReviewMolecular drivers are increasingly identified as therapeutic targets for non-small cell lung cancer (NSCLC). This review focuses on the role of ROS1 inhibitors in treating relapsed/metastatic ROS-1 altered (ROS1+) NSCLC.Recent FindingsFour FDA-approved drugs have significant activity against ROS1+ NSCLC: crizotinib, ciritinib, lorlatinib, and entrectinib. Each drug yields an overall response rates exceeding 60% with ciritinib, lorlatinib, and entrectinib possessing intracranial activity. The drugs have manageable toxicity profiles.SummaryROS1 alterations are rare molecular drivers of NSCLC that can be effectively treated with a variety of ROS1-targetd drugs. New agents are being identified that may treat resistance mutations.