New treatments have recently been introduced for treating non-small-cell lung cancer. Chemotherapeutic agents, such as pemetrexed, and targeted therapies, such as bevacizumab, erlotinib or gefitinib, have extended treatment options for selected histological subgroups. Antiangiogenic treatments, either associated with conventional chemotherapeutic drugs or given alone as maintenance therapy, constitute an active clinical research field. However, not all lung cancer patients benefit from antiangiogenic compounds. Moreover, tumour response assessment is often difficult when using these drugs, since targeted therapies generally do not cause rapid and measurable tumour shrinkage but, rather, long stabilisations and slight density changes on imaging tests. The finding of clinical or biological factors that might identify patients who will better benefit from these treatments, as well as identifying surrogate markers of tumour response and prognosis, is an issue of great interest. In that sense, different research lines have investigated the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. Circulating endothelial (CECs) and endothelial progenitor cells (CEPCs) are of prognostic value in different types of cancers, and relevant data are published about their potential usefulness as predictors of response to chemotherapy and antiangiogenic treatments. In this review, we discuss the data available on the role of CECs and CEPCs as prognostic factors and as surrogate markers of treatment response in non-small-cell lung cancer.