The recognition that inflammation plays a fundamental role in atherothrombosis has led to the measurement of circulating inflammatory biomarkers such as high-sensitivity C-reactive protein (hs-CRP) as a means of improving cardiovascular disease detection and prevention. Clinically, levels of hs-CRP >3 mg/L indicate elevated risk for myocardial infarction and stroke, even among apparently healthy individuals with low-to-normal lipid levels. Emerging laboratory and epidemiologic data now link inflammation and hs-CRP to insulin resistance in that hs-CRP levels have been associated with impaired insulin sensitivity and the development of dysglycemic conditions, including the cardiometabolic syndrome and incident type 2 diabetes. hs-CRP has also been associated with each of the individual components of the cardiometabolic syndrome. Furthermore, in large prospective studies, hs-CRP adds prognostic information about cardiovascular risk beyond that provided by the cardiometabolic syndrome. These findings have led to discussion about the addition of hs-CRP measurement to the current definition of the cardiometabolic syndrome to improve detection of risk for both diabetes and cardiovascular events in patients. Multiple clinical studies are now underway that are evaluating whether agents traditionally used to improve glycemic control may also significantly reduce hs-CRP.