Resumen: Body weight and fat content as well as enery metabolism depends on several factors such as food intake, nutrient-associated turnover, thermogenesis, and physical activity. These elements underlie complex interrelated feedback mechanisms, which are affected by personal genetic traits. A number of investigations have evidenced that not all calorie may count equal and that some specific biofactors occurring in foods may affect energy efficiency and fat deposition. Thus, the role of protein and specific amino acids, the glycemic load of different carbohydrates and foods, the type of fats, as well as the involvement of some food components with bioactive functions affecting the energy equation are being ascertained, since they can influence body composition and adiposity. Indeed, moderately high protein intake, carbohydrate with low glycemic index, n-3 fatty acids, calcium, and some thermogenic substances and antioxidants have been found to possibly contribute to reduce the body fat content. Many of these findings have been supported not only through epidemiological studies, but also by animal and cell investigations as well as through controlled nutritional interventions in humans. A better understanding of the putative involved mechanisms concerning the effects of individual fatty acids such as conjugated linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid in body composition maintenance, as well as the identification of new bioactive compounds affecting lipid turnover and energy metabolism will open the way for a better control and management of fat deposition in different stages of the life cycle, since some of them are able to control relevant metabolic pathways at the molecular level, which will contribute to precision nutrition.