Complex interactions between the brain and peripheral tissues mediate the effective control of energy balance and body weight. Hypothalamic and hindbrain neural circuits integrate peripheral signals informing the nutritional status of the animal and in response regulate nutrient intake and energy utilization. Obesity and its many medical complications emerge from the dysregulation of energy homeostasis. Excessive weight gain might also arise from alterations in reward systems of the brain that drive consumption of calorie dense, palatable foods in the absence of an energy requirement. Several neurotrophins, most notably brain-derived neurotrophic factor, have been implicated in the molecular and cellular processes underlying body weight regulation. Here, we review investigations interrogating their roles in energy balance and reward centers of the brain impacting feeding behavior and energy expenditure.