Obesity has emerged as one of the leading medical challenges of the 21st century. Obesity occurs as a result of imbalance between energy input and output and is tightly linked with metabolic diseases. Hypothalamus, a critical portion of the brain, regulates varied number of physiological processes including energy balance and nutrient metabolism. One of many theories explaining obesity proposes that weight gain is caused by dysfunction of the hypothalamic neurons that regulate energy homeostasis. A possible cause of neuronal dysfunction is inflammation. This inflammation has been implicated in leptin and insulin hormone resistance resulting defective food intake. An epidemic of obesity has forced us to evaluate the role of hypothalamic inflammation in the health implications of obesity.