Manipulation of tumor vasculature has emerged as a promising therapeutic strategy in advanced non-small cell lung cancer (NSCLC). Bevacizumab has been licensed for first-line therapy in combination with standard chemotherapy in advanced NSCLC, whereas inhibitors of platelet-derived growth factor receptors and other tyrosine kinases are currently in clinical trials for the treatment of advanced NSCLC. Perfusion computed tomography is a promising biomarker in NSCLC. As a measure of tumor perfusion and angiogenesis, perfusion computed tomography may provide invaluable pharmacodynamic information in early-phase clinical trials, monitor the vascular effects of antiangiogenic or vascular-targeting drug treatment, and provide prognostic and predictive information. Current volumetric techniques, affording a coverage of up to 28 cm, permit clinically relevant, high-quality, whole tumor evaluation.