Purpose of review: Higher serum phosphate levels are associated with adverse clinical outcomes across the spectrum of kidney function. Recent epidemiologic studies have focused on identifying potential mechanisms of these associations as well as risk factors for increased serum phosphate in the general population. Recent findings: Higher serum phosphate levels were independently associated with coronary artery calcification, vascular stiffness, left ventricular hypertrophy, and carotid artery disease, even among individuals with normal kidney function and serum phosphate levels within the normal range. Interestingly, effect modification was observed by gender in older populations, with the strength of these associations being weaker in women than in men. In addition, socioeconomic status, sex hormone levels, and common genetic variants were found to be independent predictors of serum phosphate levels, suggesting that common demographic and biological factors may predispose to higher serum phosphate in the general population. Summary: The association of increased serum phosphate with adverse outcomes may be mediated by a link between higher serum phosphate and subclinical vascular disease. Common environmental and biological factors may modulate these relationships, with potentially important implications for designing future interventional studies meant to assess the effect of lowering serum phosphate on long-term outcomes. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.