Value is a hot topic in most healthcare environments. Unfortunately, costs are frequently high in the areas of genetic testing/sequencing and molecular targeting. Surgery is another area of healthcare with traditionally high costs. There is an opportunity to help control costs while improving outcomes by bringing together molecular targeting and surgery. This is especially true in the field of vascular surgery. Molecular targeting may provide the answer as to which patients with carotid disease would benefit from surgical intervention and those to whom surgery would offer little benefit. Several promising targets include vascular cell adhesion molecule 1 (VCAM1), the class A macrophage scavenger receptor (MSR-A), matrix metalloproteinases (MMPs), and cathepsins. Other targets of interest include myeloperoxidase, fibrin, factor XIII, intercellular adhesion molecule 1, tissue factor, LOX-1, and von Willebrand factor. A VCAM1 targeting contrast medium suitable for use in humans may soon be developed. In all likelihood, a combination of molecular targets and imaging modalities may be used to stratify risk in patients with asymptomatic carotid disease. Surgery should not be overlooked as we advance our understanding of disease at the molecular or genetic level. Using molecular targeting to identify patients most likely to benefit from surgery will increase value in healthcare. The development of in vivo molecular targeting and imaging will require a substantial investment upfront, but the potential discoveries may alter the landscape of healthcare delivery for decades. While maximizing value is a laudable endeavor, we cannot sacrifice future innovation for short-term improvements in cost-efficiency.