Circulating tumor cells (CTCs) from peripheral blood have been detected in most epithelial malignancies. CTCs are very heterogeneous and can be captured via different technologies based on their physical and biological properties. The detection rates have varied depending on the technology used for enumeration. Detection, monitoring, and molecular analysis of CTCs provide a powerful and noninvasive approach for the detection of early disease, assessing prognosis and therapeutic response in cancer patients. Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies in humans. Compared with other solid tumors, the number of CTCs in NSCLC is relatively low. Nevertheless, NSCLC is a particularly important disease for CTC evaluation for prognostic purposes because of the lack of a reliable protein-based tumor marker. Molecular analyses of CTCs have provided new insights into the biology of metastasis with important implications for the clinical management of cancer patients. We review current and emerging technologies for CTC detection, with a focus on enrichment and molecular analysis of CTCs, and their potential clinical applications in NSCLC.