Currently, health beneficial roles of natural products attract much attention and diverse functional ingredients have been extensively studied their preventive effect in many diseases such as cardiovascular diseases and cancer. Squalene is one of those examples. It distributes in nature from plant to animal but extraordinarily concentrated in the liver of certain species of shark (Squalidae family) as it was first identified as a healing substance in the shark liver oil. It is now well-known that squalene is the physiological substance functioning in animal as the precursor of cholesterol biosynthesis. On the other hand, it has long history of using as an attractive resource for functional food, supplement or even pharmaceutics because it has unique physical property and wide variety of physiological functions such as anticancer and anti-hyper cholesterolemia. The antioxidant and oxygen carrying properties of squalene predicts its potential in preventing cardiovascular disease. We reviewed recent progress in functional studies of squalene both in vitro and in vivo models.