Obesity prevalence is generally higher in women than in men, and there is also a sex difference in body fat distribution. Sex differences in obesity can be explained in part by the influence of gonadal steroids on body composition and appetite; however, behavioural, socio-cultural and chromosomal factors may also play a role. This review, which evolved from the 2008 Stock Conference on sex differences in obesity, summarizes current research and recommendations related to hormonal and neuroendocrine influences on energy balance and fat distribution. A number of important gaps in the research are identified, including a need for more studies on chromosomal sex effects on energy balance, the role of socio-cultural (i.e. gender) factors in obesity and the potential deleterious effects of high-fat diets during pregnancy on the foetus. Furthermore, there is a paucity of clinical trials examining sex-specific approaches and outcomes of obesity treatment (lifestyle-based or pharmacological), and research is urgently needed to determine whether current weight loss programmes, largely developed and tested on women, are appropriate for men. Last, it is important that both animal and clinical research on obesity be designed and analysed in such a way that data can be separately examined in both men and women.