Contrast angiography is widely regarded as the gold standard investigation in peripheral artery disease (PAD). It produces images that are diagnostically valuable, but is limited by its inability to image the vessel walls or the dynamics of blood flow in the lumen. Color duplex sonography is increasingly used in PAD to replace or pre-empt angiography. It is a simple non-invasive technique that gives information about both structural and dynamic anomalies in the peripheral arteries, with an accuracy close to that of angiography. Certain situations are difficult to visualize using this technique. Arteries that are deep-lying, calcified, obscured by fat or bowel gas, or that contain low-velocity blood flow, will generate sub-optimal scans due to inadequate returning signal strength. This can be corrected by the use of microbubble echo-enhancing agents, which increase the strength of the returning signal, generating a clear image from which a diagnosis can be made. Results of multicenter studies of echo-enhanced color duplex sonography in PAD are reviewed and the impact of the technique on the diagnostic work-up of PAD is assessed.