How the brain coordinates multiple physiological and environmental signals to regulate body weight remains an important and actively investigated biological question. The answer to this question has direct clinical relevance to the management of obesity. The majority of research in this area has focused, appropriately, on neuroendocrine regulation of food intake and energy expenditure. Here we focus on recent work that builds on this progress to further expand our understanding of energy balance regulation within the context of motivated behavior. In a dynamic world, the decision to consume food is made after weighing competing needs that also must be addressed to ensure survival as individuals seek, consume and store energy. Additionally, neural systems also reward inappropriate food intake. This symposium focuses on work being done at both the circuit and systems level, in humans and animal models, to understand how and when food intake is prioritized, how the brain integrates relevant sensory information, balances competing needs, and coordinates adaptive behavior and associated physiological responses to effectively manage energy balance. This symposium will also explore development of the neural systems that accomplish these integrative processes. Additionally, we will examine how environmental and interoceptive signals, as well as neuroinflammation, can change the organization and function of these neural systems. A diverse array of experimental approaches will be on display that both support and challenge current concepts of energy balance regulation and promise to provide a rich framework for discussion and collaboration.