Investigations of the impact of physical activity on appetite control have the potential to throw light on the understanding of energy balance and therefore, upon body weight regulation and the development of obesity. Given the complexity of the landscape influencing weight regulation,research strategies should reflect this complexity. We have developed a research approach based on the concept of the psychobiological system (multi-level measurement and analysis) and an experimental platform that respects the operations of an adaptive regulating biological system. It is important that both sides of the energy balance equation (activity and diet) receive similar detailed levels of analysis. The experimental platform uses realistic and fully supervised levels of physical activity, medium-term (not acute) interventions, measurement of body composition, energy metabolism (indirect calorimetry), satiety physiology(gut peptides), homeostatic and hedonic processes of appetite control, non-exercise activity, obese adult participants and both genders. This research approach has shown that the impact of physical activity on appetite control is characterised by large individual differences. Changes in body composition, waist circumference and health benefits are more meaningful than changes in weight. Further, we are realising that the acute effects do not predict what will happen in the longer term. The psychobiological systems approach offers a strategy for simultaneously investigating biological and behavioural processes relevant to understanding obese people and how obesity can be managed. This experimental platform provides opportunities for industry to examine the impact of foods under scientifically controlled conditions relevant to the real world.