The only evidence for nutrient selection comes from baseline or treatment effects on nutrient intakes that are qualitatively similar when sensorily contrasting forms of each macronutrient are investigated and/or dietary compositions and strains of rat or mouse are different within or between laboratories. By that criterion the only potential case of a treatment reliably altering macronutrient selection identified in the present review of the literature is d-norfenfluramine, fluoxetine and paraventricular serotonin (5-HT) reducing the intake of dextrin-containing diets at early dark. The only clear example of reverse effects of an agonist and an antagonist on dietary intake was found with serotonergic agents. Claims for catecholaminergic or opioid involvement in protein intake and peptidergic involvement in carbohydrate intake were not substantiated. There remain the issues of which learnt macronutrient-specific postgastric actions and sensory cues from the affected diet rely on the neural pathway(s) on which the drug is acting to alter dietary selection. Until experiments address these questions, the neural bases of nutrient-specific appetites will remain unknown. Drug effects must be consistent across differently textured and flavoured versions of each macronutrient tested.