Recent work has advanced our knowledge of the neural pathways interfacing corticolimbic substrates of food motivation and reward with hypothalamic controls of food intake. As a neuroanatomical interface between limbic motivational processes, energy-sensing mechanisms in the mediobasal hypothalamus and motor output pathways, several studies draw attention to the lateral hypothalamus. Reviewed here are some highlights of the first session of the 11th International Symposium of the Merck-Frosst/CIHR Obesity Research Chair held in Quebec City on 5 November 2008 describing the neuroanatomical and neurochemical crosstalk between hypothalamic, midbrain and limbic sites and their role in energy balance.