Abstract: ROS1 inhibition provides impressive survival benefits in ROS1 -rearranged non-small cell lung cancer (NSCLC) patients. Crizotinib is the only tyrosine kinase inhibitor (TKI) approved by both FDA and EMA for the treatment of ROS1-positive lung cancer. In addition, several TKI have been tested with preliminary proofs of success in this oncogene-driven disease, either in the post-crizotinib setting or as first-line targeted agents. Here we present the evidence concerning entrectinib, an ALK/ROS1/NTRK inhibitor developed across different tumor types harboring rearrangements in these genes, in the context of ROS1-driven NSCLC. Of interest, in August 2019 entrectinib was granted by FDA accelerated approval for the treatment of ROS1 -rearranged NSCLC, as well as of NTRK-driven solid tumors. Keywords: lung cancer, ROS1, tyrosine kinase inhibitors, entrectinib