The role of dietary fiber in the prevention of cardiovascular disease has received increasing attention as data have accumulated. Recent cohort studies have found a consistent protective effect of dietary fiber on cardiovascular disease outcomes, prompting many leading organizations to recommend increased fiber in the daily diet. However, the biologic mechanisms explaining how a fiber influences the cardiovascular system have yet to be fully elucidated. Recent research in large national sample in the USA has demonstrated an association between dietary fiber and levels of C-reactive protein (CRP), a clinical indicator of inflammation. Epidemiologic evidence demonstrating that high-fiber diets are beneficial, coupled with this newer evidence of a possible metabolic effect on inflammatory markers, suggest that inflammation may be an important mediator in the association between dietary fiber and cardiovascular disease (CVD). This paper reviews the evidence for the connections among inflammation, CRP, dietary fiber, and CVD, and recommends further clinical studies using fiber supplementation to isolate and prospectively confirm these important relationships.