Simple SummaryThe response of living beings to adverse conditions, known as the stress reaction, is a complex mechanism including various signaling pathways and hormones. Some are evolutionarily conserved, such as the insulin signaling pathway, others, such as 20-hydroxyecdysone, adipokinetic or juvenile hormones, are taxon-specific in insects. Here we try to elucidate their interaction on theDrosophila melanogastermodel and put together all data on the subject that currently exist in the scientific literature, creating a detailed, coherent picture. We also discuss possible mechanisms which allow stress-related hormones and insulin-like peptides to regulate feeding behavior and carbohydrate and lipid metabolism inD. melanogasterimagoes under heat stress conditions.AbstractResponse to short-term stress is a fundamental survival mechanism ensuring protection and adaptation in adverse environments. Key components of the neuroendocrine stress reaction in insects are stress-related hormones, including biogenic amines (dopamine and octopamine), juvenile hormone, 20-hydroxyecdysone, adipokinetic hormone and insulin-like peptides. In this review we focus on different aspects of the mechanism of the neuroendocrine stress reaction in insects on theD. melanogastermodel, discuss the interaction of components of the insulin/insulin-like growth factors signaling pathway and other stress-related hormones, and suggest a detailed scheme of their possible interaction and effect on carbohydrate and lipid metabolism under short-term heat stress. The effect of short-term heat stress on metabolic behavior and possible regulation of its mechanisms are also discussed here.