Energy Balance (EB) is widely believed to be a central concept underlying the development and maintenance of obesity. However EB should not be conceived as a simple mechanical balance with the difference between two values translated into weight loss or gain. This static model of EB is inappropriate and the widely used rule of thumb of 8000 kcal = 1 kg body weight is false and leads to misleading expectations of weight change. The dynamic model (Hall et al, 2011; Thomas et al, 2013) provides more realistic estimates of body weight change. EB is not just a case of energy in, energy out.Ideas proposed more than 50 years ago (Edholm, 1955; 1970) but neglected until recently have led to renewed interest in the relation between EE and EI and to the interaction between physiology and behaviour. Behavioural actions (physical activity and eating) make huge contributions to EB. Edholm’s proposal that ‘the differences in intakes of food must originate in the differences in energy expenditure (Edholm et a, 1955 p 297) suggested a mechanism for the interaction between physiology and behaviour and for the role of EE in regulating appetite (EI). It is relevant that overfeeding (EI) influences EE in the form of spontaneous physical activity (Non Exercise Activity Thermogenesis – NEAT; Levine et al, 1999). Similarly, physical activity has the potential not only to influence EE but also to adjust EI. This perspective prompts a number of questions: does sedentariness downregulate EI to prevent a positive EB? Does physical activity upregulate EI in order to offset a negative EB? This raises the key issue of whether the physiological system compensates by increasing food intake when people engage in physical activity, thereby mitigating the impact of EE on weight loss.Using a multi-level systems approach it can be demonstrated that persistent daily physical activity (exercise) selectively adjusts body composition and influences components of appetite control (King et al, 2009). Moreover the two major aspects of body composition (fat mass and fat-free mass) appear to play distinct roles in appetite control with fat-free mass being a driver of meals and total daily EI (Blundell et al, 2011; 2012). A mediating role for resting metabolic rate in EI (Caudwell et al, 2013) has supported Edholm’s view that EI is related to EE. However when EE is adjusted by physical activity there is considerable individual variability in the outcomes indicating that the average response can be misleading. In principle, interactions between EE and EI can be mediated by adjustments in body composition, resting metabolic rate, substrate oxidation and by levels of tonic and episodic peptides influencing appetite. EE and EI is more than a simple question of balance.