Nature Cancer, Published online: 10 December 2025; doi:10.1038/s43018-025-01083-1Targeted therapies continue to transform the landscape of non-small-cell lung cancer (NSCLC). In 2025, the US Food and Drug Administration approved two targeted therapies, an antibody–drug conjugate and a tyrosine kinase inhibitor, for specific molecular subtypes of NSCLC. In this Clinical Outlook, we discuss their impact on the field.