Obesity is increasing at an alarming rate. The effectiveness of currently available strategies for the treatment of obesity (including pharmacologic, surgical, and behavioral interventions) is limited. Understanding the neurobiology of appetite and the important drivers of energy intake (EI) can lead to the development of more effective strategies for the prevention and treatment of obesity. Appetite regulation is complex and is influenced by genetic, social, and environmental factors. It is intricately regulated by a complex interplay of endocrine, gastrointestinal, and neural systems. Hormonal and neural signals generated in response to the energy state of the organism and the quality of food eaten are communicated by paracrine, endocrine, and gastrointestinal signals to the nervous system. The central nervous system integrates homeostatic and hedonic signals to regulate appetite. Although there has been an enormous amount of research over many decades regarding the regulation of EI and body weight, research is only now yielding potentially effective treatment strategies for obesity. The purpose of this article is to summarize the key findings presented in June 2022 at the 23rd annual Harvard Nutrition Obesity Symposium entitled "The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets." Findings presented at the symposium, sponsored by NIH P30 Nutrition Obesity Research Center at Harvard, enhance our current understanding of appetite biology, including innovative techniques used to assess and systematically manipulate critical hedonic processes, which will shape future research and the development of therapeutics for obesity prevention and treatment.