Obesity is one the major health problems of today showing an increasing prevalence among most countries. It is associated with increased risk of several diseases. The importance of early life strategies in the prevention of obesity is well established, whereas, in general, breastfed infants tend to have a lower body mass index (BMI) than formula-fed infants. There seem to be a series of behavioral and hormonal mechanisms that explain this difference. Lifestyle plays a crucial role in the development of overweight and/or obesity and targeted lifestyle modifications have an important impact on preventing obesity. In particular, sedentary behavior (viewing television, playing video games, doing cognitive work, and listening to music) and reduced overall physical activity along with shorter sleep duration promote the overconsumption of dietary macronutrients leading to obesity; at the same time physical activity or exercise in a sufficient dose seems to better facilitate long-term maintenance of new lower body weight. There is enough discussion about a potential effect of nutrients on obesity. Nevertheless, the most the crucial parameter regarding weight loss and prevention of obesity is to achieve a negative energy balance. In regard to specific diet regimes, again energy balance rather that any specific macronutrients composition and/or favoring of low glycemic index products, seems to be have a stronger effect on maintenance of lower weight after 12 months. It has to be noted, that for specific sup groups, obesity or overweight might be showing some favorable trends in survival. In particular, "obesity paradox" (OP) refers to an overall prognosis that is no worse and may even be better in some groups than non-obese patients. The OP could be explained by the fact that current classifications of obesity based on BMI may place together, in the same category, subjects with very different clinical and biochemical characteristics.