Cardiovascular biomarkers started as tools to aid with specific medical diagnoses, but are now being used broadly for screening, prognosis and monitoring of multiple diseases. Novel markers that reflect important pathophysiologic pathways are emerging regularly, although each new set of markers introduced raises many questions on how best to utilize them to improve patient outcomes. One promising approach for getting the most out of cardiovascular biomarkers is to combine multiple markers together into a multimarker panel. When each marker represents a distinct pathophysiologic pathway, the combined panel has advantages over individual biomarkers and may be useful when used in specific clinical scenarios for assessing risk, improving diagnosis or directing individualized therapy. This perspective article highlights several of the most promising biomarkers and strategies for achieving improved cardiovascular risk assessment for primary prevention of cardiovascular disease via multimarker panels.