All animals have evolved to adapt their behaviour and internal metabolism to a changing external environment in order to maintain homeostasis. Both metabolism and feeding behaviour are coordinated by hormone activity and neuromodulation, and a number of the implicated neuromodulatory systems are homologous between mammals and the important neurogenetic model Drosophila melanogaster. We hypothesized that silencing broad neuromodulatory systems would elicit systematic, cohesive changes in feeding, behavioural activity and metabolism. To test our hypothesis, we employed transgenic drivers that allowed us to inhibit large cellular sets of the dopaminergic, serotonergic, octopaminergic, tyraminergic and neuropeptide F systems. The resulting groups of genetically manipulated fly stocks were then assessed for changes in their overt behavioural response and metabolism by monitoring eleven parameters: activity, climbing ability, individual feeding, group feeding, food discovery, respiration (fed/starved), lipid content (fed/starved) and whole-body weight (fed/starved). Our data indicated that individual neuromodulatory systems can have dissociated effects on feeding behaviour, motor activity and metabolism. These results refute our original hypothesis, and instead suggest that neuromodulatory systems in D. melanogaster exert specialised functions across and within neurotransmitter cell types.