Obesity is characterized by the accumulation of excess body fat and can be conceptualized as the physical manifestation of chronic energy excess. Using the analogy of oedema, the consequence of positive fluid balance or fluid retention, obesity can be seen as the consequence of positive energy balance or calorie 'retention'. Just as the assessment of oedema requires a comprehensive assessment of factors related to fluid balance, the assessment of obesity requires a systematic assessment of factors potentially affecting energy intake, metabolism and expenditure. Rather than just identifying and describing a behaviour ('this patient eats too much'), clinicians should seek to identify the determinants of this behaviour ('why, does this patient eat too much?'). This paper provides an aetiological framework for the systematic assessment of the socio-cultural, biomedical, psychological and iatrogenic factors that influence energy input, metabolism and expenditure. The paper discusses factors that affect metabolism (age, sex, genetics, neuroendocrine factors, sarcopenia, metabolically active fat, medications, prior weight loss), energy intake (socio-cultural factors, mindless eating, physical hunger, emotional eating, mental health, medications) and activity (socio-cultural factors, physical and emotional barriers, medications). It is expected that the clinical application of this framework can help clinicians systematically assess, identify and thereby address the aetiological determinants of positive energy balance resulting in more effective obesity prevention and management.