American cranberries (Vaccinium macrocarpon) are commonly consumed as juice, dried fruit or dietary supplement and a rich source of phytochemicals, particularly A-type proanthocyanidins and anthocyanins. Cranberries are perhaps best known for their protection against urinary tract infections, a benefit that received a US FDA qualified health claim in 2020. Health benefits of cranberry products can also be extended to dental and gastrointestinal health, cardiometabolic and skin health, cognition, and cancer. In this chapter, we first review clinical evidence supporting these health benefits of cranberry consumption. We then discuss future directions in the elucidation of mechanism of actions for health benefits and approaches to maximizing bioefficacy of cranberry-related food/products. This information is anticipated to inform the development of cranberry products formulated with the most efficacious components, establish additive/synergistic interaction of cranberry components with other ingredients, and develop novel technologies that enhance the bioavailability of bioactive constituents of cranberries.