During the last two decades, the prevalence of obesity has dramatically increased in western and westernized societies. Its devastating health consequences include hypertension, cardiovascular diseases, or diabetes and make obesity the second leading cause of unnecessary deaths in the USA. As a consequence, obesity has a strong negative impact on the public health care systems. Recently emerging scientific insight has helped understanding obesity as a complex chronic disease with multiple causes. A multileveled gene–environment interaction appears to involve a substantial number of susceptibility genes, as well as associations with low physical activity levels and intake of high-calorie, low-cost, foods. Unfor- nately, therapeutic options to prevent or cure this disease are extremely limited, posing an extraordinary challenge for today’s biomedical research community. Obesity results from imbalanced energy metabolism leading to lipid storage. Only detailed understanding of the multiple molecular underpinnings of energy metabolism can provide the basis for future therapeutic options. Numerous aspects of obesity are currently studied, including the essential role of neural and endocrine control circuits, adaptive responses of catabolic and anabolic pathways, metabolic fuel sensors, regulation of appetite and satiation, sensory information processing, transcriptional control of metabolic processes, and the endocrine role of adipose tissue. These studies are predominantly fuelled by basic research on mammalian models or clinical studies, but these findings were paralleled by important insights, which have emerged from studying invertebrate models.