Recent evidence supports an association between elevation of inflammatory markers, such as C-reactive protein, and subsequent cardiovascular disease risk. The American Heart Association released guidelines in 2003 to help clinicians know when to use such markers. Because inflammatory markers are associated with diabetes, obesity, and hypertension, knowledge of the role of such markers is extremely important for prevention and chronic disease management. Newer studies published after the guidelines, and another recent review provide further documentation of the growing role of inflammation in cardiovascular risk. Based on the available literature, this article reviews the new guidelines, more recent evidence since the guidelines, and forms recommendations for primary care clinical practice.