Accumulating evidence suggests that ghrelin’s physiological role extends beyond appetite and energy balance to include reward-seeking behavior, involving a direct action at the level of the midbrain dopamine system. Indeed, central ghrelin signaling is important for animals to receive reward from addictive drugs including alcohol (1). Recently, we explored the role of the central ghrelin signaling system in food preference, food reward and food motivation. Direct injection of ghrelin into the brain ventricles or the VTA increased the intake of palatable/rewarding food. Preference for palatable food was suppressed by 7 days peripheral treatment with a GHS-R1A antagonist. The antagonist also suppressed the ability of rewarding food to condition a place preference (2). Finally, we explored motivated behavior for a food reward in an operant conditioning model (ie lever pressing for food in a progressive ratio schedule). Ghrelin increased motivated behavior for a sucrose reward when injected peripherally, icv (3) or intra-VTA but not intra-NAcc (4). By contrast, ghrelin administration to both the VTA and NAcc increased the free feeding of chow. In a state of overnight food restriction, where endogenous levels of ghrelin are increased, GHS-R1A blockade in the VTA was sufficient to decrease the motivation to work for a sugar reward. Blockade of GHS-R1A in VTA or NAcc was not sufficient, however, to reduce fasting-induced chow hyperphagia (4). Thus, the VTA but not the NAcc appears to be a direct target site for ghrelin’s effects on food motivation. In conclusion, the central ghrelin signaling system is important for food preference, food reward and food-motivated behavior.