The recent IMPROVE-IT trial clearly showed that lowering serum low-density lipoprotein cholesterol (LDL-C) concentrations via inhibiting intestinal cholesterol absorption through ezetimibe effectively lowered the number of new cardiovascular disease (CVD) events. This supports the use of other (dietary) interventions that lower serum LDL-C concentrations via comparable mechanisms such as described for plant sterol and stanol ester enriched functional foods. Therefore it is tempting to suggest that these compounds may have the same effects on CVD outcome, as described for ezetimibe in the IMPROVE-IT trial. This has however not been proven so far. A possible advantage of plant sterol and stanol ester enriched foods over ezetimibe-a typical single-target drug-is that these dietary compounds act on multiple targets, since they not only lower serum LDL-C concentrations, but also lower serum triacylglycerol (TAG) concentrations in subjects with elevated serum TAG concentrations. In addition, they might influence the functioning of our immune system via a changed activity of the regulatory T-cells. This combination of effects makes these compounds highly attractive to decrease CVD risk.