The American cranberry (Vaccinium macrocarpon) is one of the three commercially important fruits native to North America. Cranberries are a particularly rich source of phenolic phytochemicals, including phenolic acids (benzoic, hydroxycinnamic, and ellagic acids) and flavonoids (anthocyanins, flavonols, and flavan-3-ols). A growing body of evidence suggests that polyphenols, including those found in cranberries, may contribute to reducing the risk of cardiovascular disease (CVD) by increasing the resistance of LDL to oxidation, inhibiting platelet aggregation, reducing blood pressure, and via other anti-thrombotic and anti-inflammatory mechanisms. Research regarding the bioactivity of cranberries and their constituents on risk factors for CVD is reviewed.