Neuromodulators are often discussed as if particular chemicals map predictably onto particular insect behaviors. Evidence from contemporary neurophysiology instead indicates that behavioral consequences depend on where, when, and under which physiological conditions a signal acts. Biogenic amines, neuropeptides, endocrine signals, receptor context, cotransmission, circuit configuration, prior experience, and ongoing motor or motivational state can all modify the relationship between brain chemistry and action. This article develops an original non-empirical neurophysiological framework for interpreting these relationships across biological scales. The framework separates chemical signal identity from receptor and cellular context, circuit transformation, behavioral-state configuration, motivational valuation, and ecological action. Evidence from Drosophila demonstrates state-dependent reinforcement, sleep and arousal regulation, serotonergic modulation of stress-associated and social behavior, nutrient-responsive gut–brain signaling, reproductive-state-dependent dietary choice, peptide-mediated sensorimotor bias, and nonlinear cotransmission. Mosquito and honey-bee evidence broadens the ecological domain while emphasizing substantial taxonomic and laboratory-to-field transfer limits. The central argument is that neuromodulators should be interpreted as conditional regulators whose behavioral meaning emerges from interactions among signaling context, circuit state, biological history, and ecological demand rather than from transmitter identity alone. The proposed architecture is therefore not an insect-wide mechanistic law, but a framework for organizing evidence, identifying failed one-to-one interpretations, and generating comparative tests of when neurochemical changes translate into behavioral and ecological action.