Obesity results from the consumption of food in excess of bodily energy requirements, with the excess energy stored as adipose tissue. Sequelae of obesity, such as heart disease and type 2 diabetes, consistently rank among the top causes of death worldwide. The global prevalence of obesity highlights the urgency of understanding the mechanisms regulating hunger and satiety. Appetite, defined as the motivational drive to obtain food, is regulated by a complex neurocircuitry which integrates a variety of interoceptive signals to gauge nutritional state and guide appropriate levels of food-seeking. Here we review key recent developments in the identification of cell groups, neural circuits, endogenous and exogenous substances, and intracellular signaling pathways which drive hunger and satiety. We also consider particularly promising pharmacological targets for appetite modulation.