The pentraxins, C-reactive protein (CRP), serum amyloid P (SAP) and pentraxin3 (PTX3) are useful biomarkers for cardiovascular disease (CVD), particularly ischemic heart disease and heart failure, and are deeply involved in the pathogenesis of CVD linked to inflammation and innate immunity. Circulating elevated pentraxins, especially CRP and PTX3 levels can provide prognostic information for a variety of clinical settings and facilitate the diagnosis of CVD. Changes in these levels over time are also important indicators of pharmacological therapy, and may indicate the mechanisms by which pentraxins directly or indirectly affect the pathophysiology of CVD in an experimental setting. Here, we discuss major relevant findings associated with the clinical implications of CRP and PTX3 and their role in CVD.