Onion (Allium cepa L.) is one of the most widely used vegetable crops, belonging to the Liliaceae family. It is found across a wide range of latitudes and altitudes in Europe,Asia, North America, and Africa. Onions are rich in health promoting dietary flavonoids and the alk(en)yl cysteine sulfoxides (ACSOs). The anthocyanins in onion impart a red/purple color to some varieties and flavonols, such as quercetin and its derivatives, are responsible for the yellow and brown skins of many other varieties. Promising results have been obtained from both in vitro and in vivo investigations. Thus far, potential health benefits include antibacterial, antithrombotic, antiplatelet, and anti-asthmatic activities. Onions also exhibit immune modulatory, cardio-protective, nephro-protective,and anti-diabetic effects. This chapter reviews the spectrum of health protective effects and the related mechanisms of action of onion phytonutrients.