Obesity and associated plethora of diseases constitute a major public health challenge worldwide. The conjunction of profound changes in our lifestyle and a thrifty genetic that evolved in an environment of food scarcity largely explains this epidemic situation. Food abundance promotes our specific appetite for the more palatable food generally rich in lipids. It is noteworthy that this attraction for fatty food is not specific to humans. Rats and mice also spontaneously prefer lipid-rich food in a free-choice situation. Detection of lipids in food requires the presence of specific sensors located in strategic places (e.g., oral cavity, small intestine, brain) whose activation results in a modulation of the eating behavior. Recent data strongly suggest that the glycoprotein CD36 plays a significant role in this sensing system.