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IntroductionHelen at 59 years of age with a height of 170 cm and a weight of 136 kg has a BMI of 49 kg/m 2 which classifies her as being seriously obese. She is a health professional and well aware of the health risks associated with her excess weight. She is also a woman living in a society where a slim body is perceived as an essential requirement for feminine beauty and fashion. Over the years Helen has tried most non-fat diets as well as various drugs in her attempts to lose weight. Instead there has been a relentless increase in weight from 82 kg after the birth of her two children when she was 21 years old (a BMI of 28.5 kg/m 2 ) to her current weight and BMI which persists in spite of her healthy diet and not excessive kilojoules intake [1]. Helen is not alone; there are many other women who can testify to similar long term battles against excess weight gain [2,3]. Too often for some, attempts to lose weight leads to frustration, guilt and ultimately failure and a pre-occupation with food and dieting that may for some lead on to eating disorders. Women are not only more vulnerable to these psychological pressures [4], but also their intrinsic physiological make up makes them more prone to weight gain.Cheap energy dense food in generous portions that is too easily accessible and a sedentary life style in conjunction with socioeconomic factors such as food insecurity and lack of nutritional understanding are certainly important contributing factors to weight gain. But the question remains why, in any community, there are some who find it easier to remain slim, in spite of sharing the same obesogenic environment while others like Helen, a health conscious well informed professional, become increasingly obese. An accumulating body of emerging research in neuroscience and molecular biosciences confirms what many women know well from personal experience -that slimness is not simply a matter of willpower and diet and easily obtainable by all. The objective of this paper is to provide a broad-based literature search on current research in genetics, early development, environmental factors, gender and physiological pathways that regulate energy turnover and discuss how these may affect body fat storage in the body and biological vulnerability to obesity. Physiological Aspects of Obesity: Energy HomeostasisEnergy homeostasis involves complex sophisticated neurohormonal pathways that regulate energy balance and ensure adequate energy stores to meet increased demands for growth in children and it is particularly significant for women during pregnancy and lactation. This can be seen in the rapid increase in fat deposition that occurs particularly in critical periods during the human life span: prior to and during pregnancy and in the baby, prior to birth, during the first 6 months of life and prior to weaning [5]. The existence of these energy regulating mechanisms is also seen in the remarkable constancy of human weight, often over many years (and without calorie counting!) for some, and in the resistance to weight c...