Leptin resistance has been defined as reduced or absent responsiveness to the feeding and body weight inhibitory effects of the hormone in obese individuals compared with normal (lean) controls. Classically, leptin resistance has been associated with increased body fat and circulating leptin levels, and the effect is thought to contribute to the maintenance of obesity. Whereas a great deal is known about the central nervous system (CNS)3 mechanisms associated with leptin resistance, considerably less is known about the role of diet in establishing and maintaining this altered hormonal state. Recently, new data have emerged indicating that specific types of dietary sugars or fats are capable of inducing leptin resistance in the absence of elevated levels of circulating leptin and/or body fat. These findings suggest that specific macronutrients may be involved in the induction of leptin resistance prior to the development of obesity, and open the possibility that diet-induced leptin resistance may play a role in the onset of weight gain leading to obesity. This review will present new findings by 4 investigators on the role of diet in leptin resistance, including the effects of type and form of dietary sugar, the effect of dietary TG saturation, and potential metabolic and CNS mechanisms mediating these effects. These data were presented at a symposium sponsored by the ASN and held at the Experimental Biology 2012 Meeting, San Diego, CA on April 22, 2012.