© 2013 American Society for Nutrition. Disorders of phosphorus metabolism are independent risk factors for cardiovascular disease. Because excess dietary phosphorus intake is common in the general population and plays a central role in disturbances in phosphorus homeostasis, these findings have fueled interest in restricting phosphorus intake as a potential therapy for improving cardiovascular outcomes. Although experimental and observational data support this possibility, current limitations in the assessment of dietary phosphorus consumption in free-living populations and the lack of reliable biomarkers of the effects of dietary phosphorus on cardiovascular health pose major barriers to the design and conduct of trials assessing the efficacy of phosphorus restriction in improving cardiovascular health. Fibroblast growth factor 23 and Klotho are novel mediators of phosphorus metabolism that are tightly linked to dietary phosphorus intake and show promise as integrated biomarkers of phosphorus excess and its long-term health consequences. Advances in the understanding of how these hormones are associated with diet and phosphorus metabolism will likely bolster future efforts to assess the true health consequences of excess phosphorus intake and whether restricting phosphorus intake has salutary effects on cardiovascular health.