Obesity is now regarded as a global epidemic affecting both adults and children, and is associated with significant morbidity and mortality. Thus the effective management of obesity has become an important clinical focus. Therefore, an understanding of the pathways controlling appetite, satiety and food intake is critical for gaining an insight into the pathogenesis of obesity and also for the development of diagnostic tests and therapeutic agents for use in the clinical management of this condition. Over the last decade or more research using both mouse and human genetic models has elucidated the critical role of the leptin-melanocortin pathway in the hypothalamus, in regulating mammalian energy balance. In tandem with this, a clearer understanding of the regulation of gut-derived hormones and their interaction with the central nervous system has further illuminated the complex interplay between central and peripheral aspects of energy regulation. The obesity epidemic and the expanded knowledge base relating to its aetiopathogenesis have specific implications for clinical biochemistry. In particular, an increase in workload may be expected due to biochemical investigation of obesity and its co-morbidities. Moreover, advice on the in-depth investigation of complex cases of obesity may be sought, including information on newer diagnostic tests, such as serum leptin or molecular genetic analysis. There may also be a substantive role for chemical pathologists in establishing and running clinical obesity services. Finally, clinical biochemistry has a role in research pertaining to obesity and cardiometabolic risk.