Non-small cell lung cancer (NSCLC) has the highest morbidity and mortality worldwide among malignant tumors. NSCLC is a great threat to health and well-being. Biopsy is the gold standard to diagnose lung cancer, but traditional biopsy methods cannot fully reflect the true condition of tumors. There is growing evidence that a single-point biopsy fails to reveal the complete landscape of the tumor due to intratumor heterogeneity, but it is impractical to complete multiple biopsies that are separated both spatially and temporally. Liquid biopsy heralds that a new era is coming. Circulating tumor cells (CTCs) are tumor cells that circulate in the peripheral blood after being shed from primary or metastatic tumors. CTCs constitute a considerable portion of a liquid biopsy, which contributes to the diagnosis, assessment of prognosis, and therapy of NSCLC. Herein, this review discusses the technologies for detection and enrichment of CTCs as well as clinical applications involving CTCs.