Emerging evidence is elucidating how non-nutrient phytochemicals underlie the health promotion afforded by fruits and vegetables. This review focuses on Vaccinium macrocarpon, the American cranberry, compiling a comprehensive list of its known phytochemical components, and detailing their prevalence in cranberry fruit and its products. Flavonoids, especially colored anthocyanins, abundant flavonols, and unique proanthocyanidins, have attracted major research attention. Other notable active components include phenolic acids, benzoates, hydroxycinnamic acids, terpenes and organic acids. Health effects of cranberries, cranberry products, and isolated cranberry components in humans and animals, as well as in vitro, are debated. Evidence for protection from several bacterial pathogens, cancer, cardiovascular disease, and inflammation is compelling, while neuroprotection and anti-viral activity also have begun to draw new consideration. Emerging bioavailability data is considered and potential molecular mechanisms are evaluated, linking phytochemicals to health effects through their biochemical properties and reactions. Finally, the effects of processing and storage on cranberry phytochemicals is discussed, with a focus on identifying research gaps and novel means to preserve their natural, health-promoting components.