Context.-The diagnosis and treatment of non-small cell lung cancer have changed dramatically in the past few years. The discovery of activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor and the use of drugs that successfully target those mutations are among the key advances that have led to a shift in the practice of oncology and pathology, with perhaps the greatest effect on the field of cytology. Objectives.-To present the perspective of a practicing thoracic pathologist and cytopathologist on the developments that have changed practice and to place those changes in a broader context. Data Sources.-Literature review, studies undertaken or participated in by the author, and personal experience. Conclusions.-Cytologists are in an ideal position to influence appropriate testing and treatment in the era of targeted therapy. Lung pathology has led the way in the era of targeted therapy, in no small part due to cytology.