Carotid ultrasound provides quantitative measurements of carotid intima-media thickness (CIMT) that can be used to assess cardiovascular disease (CVD) risk in individuals and monitor ongoing disease progression and regression in clinical trials. It is non-invasive, rapid, reproducible, and carries no risk. Numerous epidemiological studies have established that CIMT is a marker of subclinical atherosclerosis and is associated with established CVD risk factors and with both prevalent and incident CVD. The use of CIMT in outcome trials as a surrogate or predictor of CVD outcomes is widespread. Carotid ultrasound is being employed to test the efficacy of CVD treatment in order to identify potential useful drugs earlier and to possibly speed regulatory approval. Successive trials have generated lessons learned and applied, with slow but steady improvement in CIMT measurement reproducibility.